G-protein coupled receptors

ABSTRACT

The invention provides human G-protein coupled receptors (GCREC) and polynucleotides which identify and encode GCREC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of GCREC.

TECHNICAL FIELD

[0001] This invention relates to nucleic acid and amino acid sequencesof G-protein coupled receptors and to the use of these sequences in thediagnosis, treatment, and prevention of cell proliferative,neurological, cardiovascular, gastrointestinal, autoimmuneimflammatory,and metabolic disorders, and viral infections, and in the assessment ofthe effects of exogenous compounds on the expression of nucleic acid andamino acid sequences of G-protein coupled receptors.

BACKGROUND OF THE INVENTION

[0002] Signal transduction is the general process by which cells respondto extracellular signals. Signal transduction across the plasma membranebegins with the binding of a signal molecule, e.g., a hormone,neurotransmitter, or growth factor, to a cell membrane receptor. Thereceptor, thus activated, triggers an intracellular biochemical cascadethat ends with the activation of an intracellular target molecule, suchas a transcription factor. This process of signal transduction regulatesall types of cell functions including cell proliferation,differentiation, and gene transcription. The G-protein coupled receptors(GPCRs), encoded by one of the largest families of genes yet identified,play a central role in the transduction of extracellular signals acrossthe plasma membrane. GPCRs have a proven history of being successfultherapeutic targets.

[0003] The largest subfamily of GPCRs, the olfactory receptors, are alsomembers of the rhodopsin-like GPCR family. These receptors function bytransducing odorant signals. Numerous distinct olfactory receptors arerequired to distinguish different odors. Each olfactory sensory neuronexpresses only one type of olfactory receptor, and distinct spatialzones of neurons expressing distinct receptors are found in nasalpassages. For example, the RA1c receptor which was isolated from a ratbrain library, has been shown to be limited in expression to verydistinct regions of the brain and a defined zone of the olfactoryepithelium (Raming, K. et al. (1998) Receptors Channels 6:141-151).However, the expression of olfactory-like receptors is not confined toolfactory tissues. For example, three rat genes encoding olfactory-likereceptors having typical GPCR characteristics showed expression patternsnot only in taste and olfactory tissue, but also in male reproductivetissue (Thomas, M. B. et al. (1996) Gene 178:1-5).

[0004] GPCRs are integral membrane proteins characterized by thepresence of seven hydrophobic transmembrane domains which together forma bundle of antiparallel alpha (α) helices. GPCRs range in size fromunder 400 to over 1000 amino acids (Strosberg, A. D. (1991) Eur. J.Biochem. 196:1-10; Coughlin, S. R. (1994) Curr. Opin. Cell Biol.6:191-197). The amino-terminus of a GPCR is extracellular, is ofvariable length, and is often glycosylated. The carboxy-terminus iscytoplasmic and generally phosphorylated. Extracellular loops alternatewith intracellular loops and link the transmembrane domains. Cysteinedisulfide bridges linking the second and third extracellular loops mayinteract with agonists and antagonists. The most conserved domains ofGPCRs are the transmembrane domains and the first two cytoplasmic loops.The transmembrane domains account, in part, for structural andfunctional features of the receptor. In most cases, the bundle of αhelices forms a ligand-binding pocket. The extracellular N-terminalsegment, or one or more of the three extracellular loops, may alsoparticipate in ligand binding. Ligand binding activates the receptor byinducing a conformational change in intracellular portions of thereceptor. In turn, the large, third intracellular loop of the activatedreceptor interacts with a heterotrimeric guanine nucleotide binding (G)protein complex which mediates further intracellular signalingactivities, including the activation of second messengers such as cyclicAMP (cAMP), phospholipase C, and inositol triphosphate, and theinteraction of the activated GPCR with ion channel proteins. (See, e.g.,Watson, S. and S. Arkinstall (1994) The G-protein Linked Receptor FactsBook, Academic Press, San Diego Calif., pp. 2-6; Bolander, F. F. (1994)Molecular Endocrinology, Academic Press, San Diego Calif., pp. 162-176;Baldwin, J. M. (1994) Curr. Opin. Cell Biol. 6:180-190.)

[0005] GPCRs include receptors for sensory signal mediators (e.g., lightand olfactory stimulatory molecules); adenosine, γ-aminobutyric acid(GABA), hepatocyte growth factor, melanocortins, neuropeptide Y, opioidpeptides, opsins, somatostatin, tachykinins, vasoactive intestinalpolypeptide family, and vasopressin; biogenic amines (e.g., dopamine,epinephrine and norepinephrine, histamine, glutamate (metabotropiceffect), acetylcholine (muscarinic effect), and serotonin); chemokines;lipid mediators of inflammation (e.g., prostaglandins and prostanoids,platelet activating factor, and leukotrienes); and peptide hormones(e.g., bombesin, bradykinin, calcitonin, C5a anaphylatoxin, endothelin,follicle-stimulating hormone (FSH), gonadotropic-releasing hormone(GnRH), neurokinin, and thyrotropin-releasing hormone (TRH), andoxytocin). GPCRs which act as receptors for stimuli that have yet to beidentified are known as orphan receptors.

[0006] The diversity of the GPCR family is further increased byalternative splicing. Many GPCR genes contain introns, and there arecurrently over 30 such receptors for which splice variants have beenidentified. The largest number of variations are at the proteinC-terminus. N-terminal and cytoplasmic loop variants are also frequent,while variants in the extracellular loops or transmembrane domains areless common. Some receptors have more than one site at which variancecan occur. The splicing variants appear to be functionally distinct,based upon observed differences in distribution, signaling, coupling,regulation, and ligand binding profiles (Kilpatrick, G. J. et al. (1999)Trends Pharmacol. Sci. 20:294-301).

[0007] GPCRs can be divided into three major subfamilies: therhodopsin-like, secretin-like, and metabotropic glutamate receptorsubfamilies. Members of these GPCR subfamilies share similar functionsand the characteristic seven transmembrane structure, but have divergentamino acid sequences. The largest family consists of the rhodopsin-likeGPCRs, which transmit diverse extracellular signals including hormones,neurotransmitters, and light. Rhodopsin is a photosensitive GPCR foundin animal retinas. In vertebrates, rhodopsin molecules are embedded inmembranous stacks found in photoreceptor (rod) cells. Each rhodopsinmolecule responds to a photon of light by triggering a decrease in cGMPlevels which leads to the closure of plasma membrane sodium channels. Inthis manner, a visual signal is converted to a neural impulse. Otherrhodopsin-like GPCRs are directly involved in responding toneurotransmitters. These GPCRs include the receptors for adrenaline(adrenergic receptors), acetylcholine (muscarinic receptors), adenosine,galanin, and glutamate (N-methyl-D-aspartate/NMDA receptors). (Reviewedin Watson, S. and S. Arkinstall (1994) The G-Protein Linked ReceptorFacts Book, Academic Press, San Diego Calif., pp. 7-9, 19-22, 32-35,130-131, 214-216, 221-222; Habert-Ortoli, E. et al. (1994) Proc. Natl.Acad. Sci. USA 91:9780-9783.)

[0008] The galanin receptors mediate the activity of the neuroendocrinepeptide galanin, which inhibits secretion of insulin, acetylcholine,serotonin and noradrenaline, and stimulates prolactin and growth hormonerelease. Galanin receptors are involved in feeding disorders, pain,depression, and Alzheimer's disease (Kask, K. et al (1997) Life Sci.60:1523-1533). Other nervous system rhodopsin-like GPCRs include agrowing family of receptors for lysophosphatidic acid and otherlysophospholipids, which appear to have roles in development andneuropathology (Chun, J. et al. (1999) Cell Biochem. Biophys.30:213-242).

[0009] Members of the secretin-like GPCR subfamily have as their ligandspeptide hormones such as secretin, calcitonin, glucagon, growthhormone-releasing hormone, parathyroid hormone, and vasoactiveintestinal peptide. For example, the secretin receptor responds tosecretin, a peptide hormone that stimulates the secretion of enzymes andions in the pancreas and small intestine (Watson, supra, pp. 278-283).Secretin receptors are about 450 amino acids in length and are found inthe plasma membrane of gastrointestinal cells. Binding of secretin toits receptor stimulates the production of cAMP.

[0010] Examples of secretin-like GPCRs implicated in inflammation andthe immune response include the EGF module-containing, mucin-likehormone receptor (Emr1) and CD97 receptor proteins. These GPCRs aremembers of the recently characterized EGF-TM7 receptors subfamily. Theseseven transmembrane hormone receptors exist as heterodimers in vivo andcontain between three and seven potential calcium-binding EGF-likemotifs. CD97 is predominantly expressed in leukocytes and is markedlyupregulated on activated B and T cells (McKnight, A. J. and S. Gordon(1998) J. Leukoc. Biol. 63:271-280).

[0011] The third GPCR subfamily is the metabotropic glutamate receptorfamily. Glutamate is the major excitatory neurotransmitter in thecentral nervous system. The metabotropic glutamate receptors modulatethe activity of intracellular effectors, and are involved in long-termpotentiation (Watson, supra, p. 130). The Ca²⁺-sensing receptor, whichsenses changes in the extracellular concentration of calcium ions, has alarge extracellular domain including clusters of acidic amino acidswhich may be involved in calcium binding. The metabotropic glutamatereceptor family also includes pheromone receptors, the GABAB receptors,and the taste receptors.

[0012] Other subfamilies of GPCRs include two groups of chemoreceptorgenes found in the nematodes Caenorhabditis elegans and Caenorhabditisbrigsae, which are distantly related to the mammalian olfactory receptorgenes. The yeast pheromone receptors STE2 and STE3, involved in theresponse to mating factors on the cell membrane, have their ownseven-transmembrane signature, as do the cAMP receptors from the slimemold Dictvostelium discoideum, which are thought to regulate theaggregation of individual cells and control the expression of numerousdevelopmentally-regulated genes.

[0013] GPCR mutations, which may cause loss of function or constitutiveactivation, have been associated with numerous human diseases (Coughlin,supra). For instance, retinitis pigmentosa may arise from mutations inthe rhodopsin gene. Furthermore, somatic activating mutations in thethyrotropin receptor have been reported to cause hyperfunctioningthyroid adenomas, suggesting that certain GPCRs susceptible toconstitutive activation may behave as protooncogenes (Parma, J. et al.(1993) Nature 365:649-651). GPCR receptors for the following ligandsalso contain mutations associated with human disease: luteinizinghormone (precocious puberty); vasopressin V₂ (X-linked nephrogenicdiabetes); glucagon (diabetes and hypertension); calcium(hyperparathyroidism, hypocalcuria, hypercalcemia); parathyroid hormone(short limbed dwarfism); β₃-adrenoceptor (obesity, non-insulin-dependentdiabetes mellitus); growth hormone releasing hormone (dwarfism); andadrenocorticotropin (glucocorticoid deficiency) (Wilson, S. et al.(1998) Br. J. Pharmocol. 125:1387-1392; Stadel, J. M. et al. (1997)Trends Pharmacol. Sci. 18:430-437). GPCRs are also involved indepression, schizophrenia, sleeplessness, hypertension, anxiety, stress,renal failure, and several cardiovascular disorders (Horn, F. and G.Vriend (1998) J. Mol. Med. 76:464-468).

[0014] In addition, within the past 20 years several hundred new drugshave been recognized that are directed towards activating or inhibitingGPCRs. The therapeutic targets of these drugs span a wide range ofdiseases and disorders, including cardiovascular, gastrointestinal, andcentral nervous system disorders as well as cancer, osteoporosis andendometriosis (Wilson, supra; Stadel, supra). For example, the dopamineagonist L-dopa is used to treat Parkinson's disease, while a dopamineantagonist is used to treat schizophrenia and the early stages ofHuntington's disease. Agonists and antagonists of adrenoceptors havebeen used for the treatment of asthma, high blood pressure, othercardiovascular disorders, and anxiety; muscarinic agonists are used inthe treatment of glaucoma and tachycardia; serotonin 5HT1D antagonistsare used against migraine; and histamine H1 antagonists are used againstallergic and anaphylactic reactions, hay fever, itching, and motionsickness (Horn, supra).

[0015] Recent research suggests potential future therapeutic uses forGPCRs in the treatment of metabolic disorders including diabetes,obesity, and osteoporosis. For example, mutant V2 vasopressin receptorscausing nephrogenic diabetes could be functionally rescued in vitro byco-expression of a C-terminal V2 receptor peptide spanning the regioncontaining the mutations. This result suggests a possible novel strategyfor disease treatment (Schöneberg, T. et al. (1996) EMBO J.15:1283-1291). Mutations in melanocortin-4 receptor (MC4R) areimplicated in human weight regulation and obesity. As with thevasopressin V2 receptor mutants, these MC4R mutants are defective intrafficking to the plasma membrane (Ho, G. and R. G. MacKenzie (1999) J.Biol. Chem. 274:35816-35822), and thus might be treated with a similarstrategy. The type 1 receptor for parathyroid hormone (PTH) is a GPCRthat mediates the PTH-dependent regulation of calcium homeostasis in thebloodstream. Study of PTH receptor interactions may enable thedevelopment of novel PTH receptor ligands for the treatment ofosteoporosis (Mannstadt, M. et al. (1999) Am. J. Physiol.277:F665-F675).

[0016] The chemokine receptor group of GPCRs have potential therapeuticutility in inflammation and infectious disease. (For review, see Locati,M. and P. M. Murphy (1999) Annu. Rev. Med. 50:425-440.) Chemokines aresmall polypeptides that act as intracellular signals in the regulationof leukocyte trafficking, hematopoiesis, and angiogenesis. Targeteddisruption of various chemokine receptors in mice indicates that thesereceptors play roles in pathologic inflammation and in autoimmunedisorders such as multiple sclerosis. Chemokine receptors are alsoexploited by infectious agents, including herpesviruses and the humanimmunodeficiency virus (HIV-1) to facilitate infection. A truncatedversion of chemokine receptor CCR5, which acts as a coreceptor forinfection of T-cells by HIV-1, results in resistance to AIDS, suggestingthat CCR5 antagonists could be useful in preventing the development ofAIDS.

[0017] The netrins are a family of molecules that function as diffusibleattractants and repellants to guide migrating cells and axons to theirtargets within the developing nervous system. The netrin receptorsinclude the C. elegans protein UNC-5, as well as homologues recentlyidentified in vertebrates (Leonardo, E. D. et al. (1997) Nature386:833-838). These receptors are members of the immunoglobulinsuperfamily, and also contain a characteristic domain called the ZU5domain. Mutations in the mouse member of the netrin receptor family, Rcm(rostral cerebellar malformation) result in cerebellar and midbraindefects as an apparent result of abnormal neuronal migration (Ackerman,S. L. et al. (1997) Nature 386:838-842).

[0018] Expression Profiling

[0019] Array technology can provide a simple way to explore theexpression of a single polymorphic gene or the expression profile of alarge number of related or unrelated genes. When the expression of asingle gene is examined, arrays are employed to detect the expression ofa specific gene or its variants. When an expression profile is examined,arrays provide a platform for identifying genes that are tissuespecific, are affected by a substance being tested in a toxicologyassay, are part of a signaling cascade, carry out housekeepingfunctions, or are specifically related to a particular geneticpredisposition, condition, disease, or disorder.

[0020] IL-S Treatment and Immune Response

[0021] Cells undergoing neoplastic growth gradually progress to invasivecarcinoma and become metastatic. Factors involved in tumor progressionand malignant transformation include genetic factors, environmentalfactors, growth factors, and hormones. Histological and molecularevaluation of breast tumors has revealed that the development of breastcancer evolves through a multi-step process whereby pre-malignantmammary epithelial cells undergo a relatively defined sequence of eventsleading to tumor formation.

[0022] Neoplastic growth is mediated by a variety of factors such asInterleukin 5 (IL-5), a T cell-derived factor that promotes theproliferation, differentiation, and activation of eosinophils. IL-5 hasalso been known as T cell replacing factor (TRF), B cell growth factorII (BCGFII), B cell differentiation factor m (BCDF m), eosinophildifferentiation factor (EDF), and eosinophil colony-stimulating factor(Bo-CSF). IL-5 exerts its activity on target cells by binding tospecific cell surface receptors. The effect of IL-5 may be observed inhuman peripheral blood mononuclear cells (PBMCs), which contain about52% lymphocytes (12% B lymphocytes, 40% T lymphocytes (25% CD4+ and 15%CD8+)), 20% NK cells, 25% monocytes, and 3% various cells that includedendritic cells and progenitor cells.

[0023] The discovery of new G-protein coupled receptors, and thepolynucleotides encoding them, satisfies a need in the art by providingnew compositions which are useful in the diagnosis, prevention, andtreatment of cell proliferative, neurological, cardiovascular,gastrointestinal, autoimmune/inflammatory, and metabolic disorders, andviral infections, and in the assessment of the effects of exogenouscompounds on the expression of nucleic acid and amino acid sequences ofG-protein coupled receptors.

SUMMARY OF THE INVENTION

[0024] The invention features purified polypeptides, G-protein coupledreceptors, referred to collectively as “GCREC” and individually as“GCREC-1,” “GCREC-2,” “GCREC-3,” “GCREC-4,” “GCREC-5,” “GCREC-6,”“GCREC-7,” “GCREC-8,” “GCREC-9,” “GCREC-10,” “GCREC-11,” “GCREC-12,”“GCREC-13,” “GCREC-14,” “GCREC-15,” “GCREC-16,” “GCREC-17,” “GCREC-18,”“GCREC-19,” “GCREC-20,” “GCREC-21,” “GCREC-22,” “GCREC-23,” “GCREC-24,”“GCREC-25,” “GCREC-26,” “GCREC-27,” “GCREC-28,” “GCREC-29,” “GCREC-30,”“GCREC-31,” “GCREC-32,” “GCREC-33,” “GCREC-34,” “GCREC-35,” “GCREC-36,”“GCREC-37,” “GCREC-38,” “GCREC-39,” “GCREC-40,” “GCREC-41,” “GCREC-42,”“GCREC-43,” “GCREC-44,” “GCREC-45,” “GCREC-46,” “GCREC-47,” “GCREC-48,”“GCREC-49,” “GCREC-50,” “GCREC-51,” “GCREC-52,” “GCREC-53,” “GCREC-54,”“GCREC-55,” “GCREC-56,” “GCREC-57,” “GCREC-58,” “GCREC-59,” “GCREC-60,”“GCREC-61,” “GCREC-62,” “GCREC-63,” “GCREC-64,” “GCREC-65,” “GCREC-66,”“GCREC-67,”“GCREC-68,” “GCREC-69,” “GCREC-70,” “GCREC-71,” “GCREC-72,”and “GCREC-73.” In one aspect, the invention provides an isolatedpolypeptide selected from the group consisting of a) a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-73, b) a polypeptide comprising a naturally occurring aminoacid sequence at least 90% identical to an amino acid sequence selectedfrom the group consisting of SEQ ID NO:1-73, c) a biologically activefragment of a polypeptide having an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-73, and d) an immunogenic fragmentof a polypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73. In one alternative, the invention providesan isolated polypeptide comprising the amino acid sequence of SEQ IDNO:1-73.

[0025] The invention further provides an isolated polynucleotideencoding a polypeptide selected from the group consisting of a) apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, b) a polypeptide comprising a naturallyoccurring amino acid sequence at least 90% identical to an amino acidsequence selected from the group consisting of SEQ ID NO:1-73, c) abiologically active fragment of a polypeptide having an amino acidsequence selected from the group consisting of SEQ ID NO:1-73, and d) animmunogenic fragment of a polypeptide having an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73. In onealternative, the polynucleotide encodes a polypeptide selected from thegroup consisting of SEQ ID NO:1-73. In another alternative, thepolynucleotide is selected from the group consisting of SEQ IDNO:74-146.

[0026] Additionally, the invention provides a recombinant polynucleotidecomprising a promoter sequence operably linked to a polynucleotideencoding a polypeptide selected from the group consisting of a) apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, b) a polypeptide comprising a naturallyoccurring amino acid sequence at least 90% identical to an amino acidsequence selected from the group consisting of SEQ ID NO:1-73, c) abiologically active fragment of a polypeptide having an amino acidsequence selected from the group consisting of SEQ ID NO:1-73, and d) animmunogenic fragment of a polypeptide having an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73. In onealternative, the invention provides a cell transformed with therecombinant polynucleotide. In another alternative, the inventionprovides a transgenic organism comprising the recombinantpolynucleotide.

[0027] The invention also provides a method for producing a polypeptideselected from the group consisting of a) a polypeptide comprising anamino acid sequence selected from the group consisting of SEQ IDNO:1-73, b) a polypeptide comprising a naturally occurring amino acidsequence at least 90% identical to an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-73, c) a biologically activefragment of a polypeptide having an amino acid sequence selected fromthe group consisting of SEQ ID NO:1-73, and d) an immunogenic fragmentof a polypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73. The method comprises a) culturing a cellunder conditions suitable for expression of the polypeptide, whereinsaid cell is transformed with a recombinant polynucleotide comprising apromoter sequence operably linked to a polynucleotide encoding thepolypeptide, and b) recovering the polypeptide so expressed.

[0028] Additionally, the invention provides an isolated antibody whichspecifically binds to a polypeptide selected from the group consistingof a) a polypeptide comprising an amino acid sequence selected from thegroup consisting of SEQ ID NO:1-73, b) a polypeptide comprising anaturally occurring amino acid sequence at least 90% identical to anamino acid sequence selected from the group consisting of SEQ IDNO:1-73, c) a biologically active fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73, and d) an immunogenic fragment of a polypeptide having an aminoacid sequence selected from the group consisting of SEQ ID NO:1-73.

[0029] The invention further provides an isolated polynucleotideselected from the group consisting of a) a polynucleotide comprising apolynucleotide sequence selected from the group consisting of SEQ IDNO:74-146, b) a polynucleotide comprising a naturally occurringpolynucleotide sequence at least 90% identical to a polynucleotidesequence selected from the group consisting of SEQ ID NO:74-146, c) apolynucleotide complementary to the polynucleotide of a), d) apolynucleotide complementary to the polynucleotide of b), and e) an RNAequivalent of a)-d). In one alternative, the polynucleotide comprises atleast 60 contiguous nucleotides.

[0030] Additionally, the invention provides a method for detecting atarget polynucleotide in a sample, said target polynucleotide having asequence of a polynucleotide selected from the group consisting of a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:74-146, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:74-146, c) a polynucleotide complementary to the polynucleotide ofa), d) a polynucleotide complementary to the polynucleotide of b), ande) an RNA equivalent of a)-d). The method comprises a) hybridizing thesample with a probe comprising at least 20 contiguous nucleotidescomprising a sequence complementary to said target polynucleotide in thesample, and which probe specifically hybridizes to said targetpolynucleotide, under conditions whereby a hybridization complex isformed between said probe and said target polynucleotide or fragmentsthereof, and b) detecting the presence or absence of said hybridizationcomplex, and optionally, if present, the amount thereof. In onealternative, the probe comprises at least 60 contiguous nucleotides.

[0031] The invention further provides a method for detecting a targetpolynucleotide in a sample, said target polynucleotide having a sequenceof a polynucleotide selected from the group consisting of a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:74-146, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:74-146, c) a polynucleotide complementary to the polynucleotide ofa), d) a polynucleotide complementary to the polynucleotide of b), ande) an RNA equivalent of a)-d). The method comprises a) amplifying saidtarget polynucleotide or fragment thereof using polymerase chainreaction amplification, and b) detecting the presence or absence of saidamplified target polynucleotide or fragment thereof, and, optionally, ifpresent, the amount thereof.

[0032] The invention further provides a composition comprising aneffective amount of a polypeptide selected from the group consisting ofa) a polypeptide comprising an amino acid sequence selected from thegroup consisting of SEQ ID NO:1-73, b) a polypeptide comprising anaturally occurring amino acid sequence at least 90% identical to anamino acid sequence selected from the group consisting of SEQ IDNO:1-73, c) a biologically active fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73, and d) an immunogenic fragment of a polypeptide having an aminoacid sequence selected from the group consisting of SEQ ID NO:1-73, anda pharmaceutically acceptable excipient. In one embodiment, thecomposition comprises an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73. The invention additionally provides amethod of treating a disease or condition associated with decreasedexpression of functional GCREC, comprising administering to a patient inneed of such treatment the composition.

[0033] The invention also provides a method for screening a compound foreffectiveness as an agonist of a polypeptide selected from the groupconsisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-73, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-73, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73. The method comprises a) exposing a sample comprising thepolypeptide to a compound, and b) detecting agonist activity in thesample. In one alternative, the invention provides a compositioncomprising an agonist compound identified by the method and apharmaceutically acceptable excipient. In another alternative, theinvention provides a method of treating a disease or conditionassociated with decreased expression of functional GCREC, comprisingadministering to a patient in need of such treatment the composition.

[0034] Additionally, the invention provides a method for screening acompound for effectiveness as an antagonist of a polypeptide selectedfrom the group consisting of a) a polypeptide comprising an amino acidsequence selected from the group consisting of SEQ ID NO:1-73, b) apolypeptide comprising a naturally occurring amino acid sequence atleast 90% identical to an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, c) a biologically active fragment of apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, and d) an immunogenic fragment of apolypeptide having an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73. The method comprises a) exposing a samplecomprising the polypeptide to a compound, and b) detecting antagonistactivity in the sample. In one alternative, the invention provides acomposition comprising an antagonist compound identified by the methodand a pharmaceutically acceptable excipient. In another alternative, theinvention provides a method of treating a disease or conditionassociated with overexpression of functional GCREC, comprisingadministering to a patient in need of such treatment the composition.

[0035] The invention further provides a method of screening for acompound that specifically binds to a polypeptide selected from thegroup consisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-73, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-73, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73. The method comprises a) combining the polypeptide with at leastone test compound under suitable conditions, and b) detecting binding ofthe polypeptide to the test compound, thereby identifying a compoundthat specifically binds to the polypeptide.

[0036] The invention further provides a method of screening for acompound that modulates the activity of a polypeptide selected from thegroup consisting of a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-73, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-73, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73. The method comprises a) combining the polypeptide with at leastone test compound under conditions permissive for the activity of thepolypeptide, b) assessing the activity of the polypeptide in thepresence of the test compound, and c) comparing the activity of thepolypeptide in the presence of the test compound with the activity ofthe polypeptide in the absence of the test compound, wherein a change inthe activity of the polypeptide in the presence of the test compound isindicative of a compound that modulates the activity of the polypeptide.

[0037] The invention further provides a method for screening a compoundfor effectiveness in altering expression of a target polynucleotide,wherein said target polynucleotide comprises a polynucleotide sequenceselected from the group consisting of SEQ ID NO:74-146, the methodcomprising a) exposing a sample comprising the target polynucleotide toa compound, b) detecting altered expression of the targetpolynucleotide, and c) comparing the expression of the targetpolynucleotide in the presence of varying amounts of the compound and inthe absence of the compound.

[0038] The invention further provides a method for assessing toxicity ofa test compound, said method comprising a) treating a biological samplecontaining nucleic acids with the test compound; b) hybridizing thenucleic acids of the treated biological sample with a probe comprisingat least 20 contiguous nucleotides of a polynucleotide selected from thegroup consisting of i) a polynucleotide comprising a polynucleotidesequence selected from the group consisting of SEQ ID NO:74-146, ii) apolynucleotide comprising a naturally occurring polynucleotide sequenceat least 90% identical to a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:74-146, iii) a polynucleotide having asequence complementary to i), iv) a polynucleotide complementary to thepolynucleotide of ii), and v) an RNA equivalent of i)-iv). Hybridizationoccurs under conditions whereby a specific hybridization complex isformed between said probe and a target polynucleotide in the biologicalsample, said target polynucleotide selected from the group consisting ofi) a polynucleotide comprising a polynucleotide sequence selected fromthe group consisting of SEQ ID NO:74-146, ii) a polynucleotidecomprising a naturally occurring polynucleotide sequence at least 90%identical to a polynucleotide'sequence selected from the groupconsisting of SEQ ID NO:74-146, iii) a polynucleotide complementary tothe polynucleotide of i), iv) a polynucleotide complementary to thepolynucleotide of ii), and v) an RNA equivalent of i)-iv).Alternatively, the target polynucleotide comprises a fragment of apolynucleotide sequence selected from the group consisting of i)-v)above; c) quantifying the amount of hybridization complex; and d)comparing the amount of hybridization complex in the treated biologicalsample with the amount of hybridization complex in an untreatedbiological sample, wherein a difference in the amount of hybridizationcomplex in the treated biological sample is indicative of toxicity ofthe test compound.

BRIEF DESCRIPTION OF THE TABLES

[0039] Table 1 summarizes the nomenclature for the full lengthpolynucleotide and polypeptide sequences of the present invention.

[0040] Table 2 shows the GenBank identification number and annotation ofthe nearest GenBank homolog for polypeptides of the invention. Theprobability scores for the matches between each polypeptide and itshomolog(s) are also shown.

[0041] Table 3 shows structural features of polypeptide sequences of theinvention, including predicted motifs and domains, along with themethods, algorithms, and searchable databases used for analysis of thepolypeptides.

[0042] Table 4 lists the cDNA and/or genomic DNA fragments which wereused to assemble polynucleotide sequences of the invention, along withselected fragments of the polynucleotide sequences.

[0043] Table 5 shows the representative cDNA library for polynucleotidesof the invention.

[0044] Table 6 provides an appendix which describes the tissues andvectors used for construction of the cDNA libraries shown in Table 5.

[0045] Table 7 shows the tools, programs, and algorithms used to analyzethe polynucleotides and polypeptides of the invention, along withapplicable descriptions, references, and threshold parameters.

DESCRIPTION OF THE INVENTION

[0046] Before the present proteins, nucleotide sequences, and methodsare described, it is understood that this invention is not limited tothe particular machines, materials and methods described, as these mayvary. It is also to be understood that the terminology used herein isfor the purpose of describing particular embodiments only, and is notintended to limit the scope of the present invention which will belimited only by the appended claims.

[0047] It must be noted that as used herein and in the appended claims,the singular forms “a,” “an,” and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, a referenceto “a host cell” includes a plurality of such host cells, and areference to “an antibody” is a reference to one or more antibodies andequivalents thereof known to those skilled in the art, and so forth.

[0048] Unless defined otherwise, all technical and scientific terms usedherein have the same meanings as commonly understood by one of ordinaryskill in the art to which this invention belongs. Although any machines,materials, and methods similar or equivalent to those described hereincan be used to practice or test the present invention, the preferredmachines, materials and methods are now described. All publicationsmentioned herein are cited for the purpose of describing and disclosingthe cell lines, protocols, reagents and vectors which are reported inthe publications and which might be used in connection with theinvention. Nothing herein is to be construed as an admission that theinvention is not entitled to antedate such disclosure by virtue of priorinvention.

[0049] Definitions

[0050] “GCREC” refers to the amino acid sequences of substantiallypurified GCREC obtained from any species, particularly a mammalianspecies, including bovine, ovine, porcine, murine, equine, and human,and from any source, whether natural, synthetic, semi-synthetic, orrecombinant.

[0051] The term “agonist” refers to a molecule which intensifies ormimics the biological activity of GCREC. Agonists may include proteins,nucleic acids, carbohydrates, small molecules, or any other compound orcomposition which modulates the activity of GCREC either by directlyinteracting with GCREC or by acting on components of the biologicalpathway in which GCREC participates.

[0052] An “allelic variant” is an alternative form of the gene encodingGCREC. Allelic variants may result from at least one mutation in thenucleic acid sequence and may result in altered mRNAs or in polypeptideswhose structure or function may or may not be altered. A gene may havenone, one, or many allelic variants of its naturally occurring form.Common mutational changes which give rise to allelic variants aregenerally ascribed to natural deletions, additions, or substitutions ofnucleotides. Each of these types of changes may occur alone, or incombination with the others, one or more times in a given sequence.

[0053] “Altered” nucleic acid sequences encoding GCREC include thosesequences with deletions, insertions, or substitutions of differentnucleotides, resulting in a polypeptide the same as GCREC or apolypeptide with at least one functional characteristic of GCREC.Included within this definition are polymorphisms which may or may notbe readily detectable using a particular oligonucleotide probe of thepolynucleotide encoding GCREC, and improper or unexpected hybridizationto allelic variants, with a locus other than the normal chromosomallocus for the polynucleotide sequence encoding GCREC. The encodedprotein may also be “altered,” and may contain deletions, insertions, orsubstitutions of amino acid residues which produce a silent change andresult in a functionally equivalent GCREC. Deliberate amino acidsubstitutions may be made on the basis of similarity in polarity,charge, solubility, hydrophobicity, hydrophilicity, and/or theamphipathic nature of the residues, as long as the biological orimmunological activity of GCREC is retained. For example, negativelycharged amino acids may include aspartic acid and glutamic acid, andpositively charged amino acids may include lysine and arginine. Aminoacids with uncharged polar side chains having similar hydrophilicityvalues may include: asparagine and glutamine; and serine and threonine.Amino acids with uncharged side chains having similar hydrophilicityvalues may include: leucine, isoleucine, and valine; glycine andalanine; and phenylalanine and tyrosine.

[0054] The terms “amino acid” and “amino acid sequence” refer to anoligopeptide, peptide, polypeptide, or protein sequence, or a fragmentof any of these, and to naturally occurring or synthetic molecules.Where “amino acid sequence” is recited to refer to a sequence of anaturally occurring protein molecule, “amino acid sequence” and liketerms are not meant to limit the amino acid sequence to the completenative amino acid sequence associated with the recited protein molecule.

[0055] “Amplification” relates to the production of additional copies ofa nucleic acid sequence. Amplification is generally carried out usingpolymerase chain reaction (PCR) technologies well known in the art.

[0056] The term “antagonist” refers to a molecule which inhibits orattenuates the biological activity of GCREC. Antagonists may includeproteins such as antibodies, nucleic acids, carbohydrates, smallmolecules, or any other compound or composition which modulates theactivity of GCREC either by directly interacting with GCREC or by actingon components of the biological pathway in which GCREC participates.

[0057] The term “antibody” refers to intact immunoglobulin molecules aswell as to fragments thereof, such as Fab, F(ab′)₂, and Fv fragments,which are capable of binding an epitopic determinant. Antibodies thatbind GCREC polypeptides can be prepared using intact polypeptides orusing fragments containing small peptides of interest as the immunizingantigen. The polypeptide or oligopeptide used to immunize an animal(e.g., a mouse, a rat, or a rabbit) can be derived from the translationof RNA, or synthesized chemically, and can be conjugated to a carrierprotein if desired. Commonly used carriers that are chemically coupledto peptides include bovine serum albumin, thyroglobulin, and keyholelimpet hemocyanin (KLI). The coupled peptide is then used to immunizethe animal.

[0058] The term “antigenic determinant” refers to that region of amolecule (i.e., an epitope) that makes contact with a particularantibody. When a protein or a fragment of a protein is used to immunizea host animal, numerous regions of the protein may induce the productionof antibodies which bind specifically to antigenic determinants(particular regions or three-dimensional structures on the protein). Anantigenic determinant may compete with the intact antigen (i.e., theimmunogen used to elicit the immune response) for binding to anantibody.

[0059] The term “aptamer” refers to a nucleic acid or oligonucleotidemolecule that binds to a specific molecular target. Aptamers are derivedfrom an in vitro evolutionary process (e.g., SELEX (Systematic Evolutionof Ligands by EXponential Enrichment), described in U.S. Pat. No.5,270,163), which selects for target-specific aptamer sequences fromlarge combinatorial libraries. Aptamer compositions may bedouble-stranded or single-stranded, and may includedeoxyribonucleotides, ribonucleotides, nucleotide derivatives, or othernucleotide-like molecules. The nucleotide components of an aptamer mayhave modified sugar groups (e.g., the 2′-OH group of a ribonucleotidemay be replaced by 2′-F or 2′-NH₂), which may improve a desiredproperty, e.g., resistance to nucleases or longer lifetime in blood.Aptamers may be conjugated to other molecules, e.g., a high molecularweight carrier to slow clearance of the aptamer from the circulatorysystem. Aptamers may be specifically cross-linked to their cognateligands, e.g., by photo-activation of a cross-linker. (See, e.g., Brody,E. N. and L. Gold (2000) J. Biotechnol. 74:5-13.)

[0060] The term “intramer” refers to an aptamer which is expressed invivo. For example, a vaccinia virus-based RNA expression system has beenused to express specific RNA aptamers at high levels in the cytoplasm ofleukocytes (Blind, M. et al. (1999) Proc. Natl Acad. Sci. USA96:3606-3610).

[0061] The term “spiegelmer” refers to an aptamer which includes L-DNA,L-RNA, or other left-handed nucleotide derivatives or nucleotide-likemolecules. Aptamers containing left-handed nucleotides are resistant todegradation by naturally occurring enzymes, which normally act onsubstrates containing right-handed nucleotides.

[0062] The term “antisense” refers to any composition capable ofbase-pairing with the “sense” (coding) strand of a specific nucleic acidsequence. Antisense compositions may include DNA; RNA; peptide nucleicacid (PNA); oligonucleotides having modified backbone linkages such asphosphorothioates, methylphosphonates, or benzylphosphonates;oligonucleotides having modified sugar groups such as 2′-methoxyethylsugars or 2′-methoxyethoxy sugars; or oligonucleotides having modifiedbases such as 5-methyl cytosine, 2′-deoxyuracil, or7-deaza-2′-deoxyguanosine. Antisense molecules may be produced by anymethod including chemical synthesis or transcription. Once introducedinto a cell, the complementary antisense molecule base-pairs with anaturally occurring nucleic acid sequence produced by the cell to formduplexes which block either transcription or translation The designation“negative” or “inus” can refer to the antisense strand, and thedesignation “positive” or “plus” can refer to the sense strand of areference DNA molecule.

[0063] The term “biologically active” refers to a protein havingstructural, regulatory, or biochemical functions of a naturallyoccurring molecule. Likewise, “immunologically active” or “immunogenic”refers to the capability of the natural, recombinant, or syntheticGCREC, or of any oligopeptide thereof, to induce a specific immuneresponse in appropriate animals or cells and to bind with specificantibodies.

[0064] “Complementary” describes the relationship between twosingle-stranded nucleic acid sequences that anneal by base-pairing. Forexample, 5′-AGT-3′ pairs with its complement, 3′-TCA-5′.

[0065] A “composition comprising a given polynucleotide sequence” and a“composition comprising a given amino acid sequence” refer broadly toany composition containing the given polynucleotide or amino acidsequence. The composition may comprise a dry formulation or an aqueoussolution. Compositions comprising polynucleotide sequences encodingGCREC or fragments of GCREC may be employed as hybridization probes. Theprobes may be stored in freeze-dried form and may be associated with astabilizing agent such as a carbohydrate. In hybridizations, the probemay be deployed in an aqueous solution containing salts (e.g., NaCl),detergents (e.g., sodium dodecyl sulfate; SDS), and other components(e.g., Denhardt's solution, dry milk, salmon sperm DNA, etc.).

[0066] “Consensus sequence” refers to a nucleic acid sequence which hasbeen subjected to repeated DNA sequence analysis to resolve uncalledbases, extended using the XL-PCR kit (Applied Biosystems, Foster CityCalif.) in the 5′ and/or the 3′ direction, and resequenced, or which hasbeen assembled from one or more overlapping cDNA, EST, or genomic DNAfragments using a computer program for fragment assembly, such as theGELVIEW fragment assembly system (GCG, Madison Wis.) or Phrap(University of Washington, Seattle Wash.). Some sequences have been bothextended and assembled to produce the consensus sequence.

[0067] “Conservative amino acid substitutions” are those substitutionsthat are predicted to least interfere with the properties of theoriginal protein, i.e., the structure and especially the function of theprotein is conserved and not significantly changed by suchsubstitutions. The table below shows amino acids which may besubstituted for an original amino acid in a protein and which areregarded as conservative amino acid substitutions. Original ResidueConservative Substitution Ala Gly, Ser Arg His, Lys Asn Asp, Gln, HisAsp Asn, Glu Cys Ala, Ser Gln Asn, Glu, His Glu Asp, Gln, His Gly AlaHis Asn, Arg, Gln, Glu Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu MetLeu, Ile Phe His, Met, Leu, Trp, Tyr Ser Cys, Thr Thr Ser, Val Trp Phe,Tyr Tyr His, Phe, Trp Val Ile, Leu, Thr

[0068] Conservative amino acid substitutions generally maintain (a) thestructure of the polypeptide backbone in the area of the substitution,for example, as a beta sheet or alpha helical conformation, (b) thecharge or hydrophobicity of the molecule at the site of thesubstitution, and/or (c) the bulk of the side chain.

[0069] A “deletion” refers to a change in the amino acid or nucleotidesequence that results in the absence of one or more amino acid residuesor nucleotides.

[0070] The term “derivative” refers to a chemically modifiedpolynucleotide or polypeptide. Chemical modifications of apolynucleotide can include, for example, replacement of hydrogen by analkyl, acyl, hydroxyl, or amino group. A derivative polynucleotideencodes a polypeptide which retains at least one biological orimmunological function of the natural molecule. A derivative polypeptideis one modified by glycosylation, pegylation, or any similar processthat retains at least one biological or immunological function of thepolypeptide from which it was derived.

[0071] A “detectable label” refers to a reporter molecule or enzyme thatis capable of generating a measurable signal and is covalently ornoncovalently joined to a polynucleotide or polypeptide.

[0072] “Differential expression” refers to increased or upregulated; ordecreased, downregulated, or absent gene or protein expression,determined by comparing at least two different samples. Such comparisonsmay be carried out between, for example, a treated and an untreatedsample, or a diseased and a normal sample.

[0073] “Exon shuffling” refers to the recombination of different codingregions (exons). Since an exon may represent a structural or functionaldomain of the encoded protein, new proteins may be assembled through thenovel reassortment of stable substructures, thus allowing accelerationof the evolution of new protein functions.

[0074] A “fragment” is a unique portion of GCREC or the polynucleotideencoding GCREC which is identical in sequence to but shorter in lengththan the parent sequence. A fragment may comprise up to the entirelength of the defined sequence, minus one nucleotide/amino acid residue.For example, a fragment may comprise from 5 to 1000 contiguousnucleotides or amino acid residues. A fragment used as a probe, primer,antigen, therapeutic molecule, or for other purposes, maybe at least 5,10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500contiguous nucleotides or amino acid residues in length. Fragments maybe preferentially selected from certain regions of a molecule. Forexample, a polypeptide fragment may comprise a certain length ofcontiguous amino acids selected from the first 250 or 500 amino acids(or first 25% or 50%) of a polypeptide as shown in a certain definedsequence. Clearly these lengths are exemplary, and any length that issupported by the specification, including the Sequence Listing, tables,and figures, may be encompassed by the present embodiments.

[0075] A fragment of SEQ ID NO:74-146 comprises a region of uniquepolynucleotide sequence that specifically identifies SEQ ID NO:74-146,for example, as distinct from any other sequence in the genome fromwhich the fragment was obtained. A fragment of SEQ ID NO:74-146 isuseful, for example, in hybridization and amplification technologies andin analogous methods that distinguish SEQ ID NO:74-146 from relatedpolynucleotide sequences. The precise length of a fragment of SEQ IDNO:74-146 and the region of SEQ ID NO:74-146 to which the fragmentcorresponds are routinely determinable by one of ordinary skill in theart based on the intended purpose for the fragment.

[0076] A fragment of SEQ ID NO:1-73 is encoded by a fragment of SEQ IDNO:74-146. A fragment of SEQ ID NO:1-73 comprises a region of uniqueamino acid sequence that specifically identifies SEQ ID NO:1-73. Forexample, a fragment of SEQ ID NO:1-73 is useful as an immunogenicpeptide for the development of antibodies that specifically recognizeSEQ ID NO:1-73. The precise length of a fragment of SEQ ID NO:1-73 andthe region of SEQ ID NO:1-73 to which the fragment corresponds areroutinely determinable by one of ordinary skill in the art based on theintended purpose for the fragment.

[0077] A “full length” polynucleotide sequence is one containing atleast a translation initiation codon (e.g., methionine) followed by anopen reading frame and a translation termination codon. A “full length”polynucleotide sequence encodes a “full length” polypeptide sequence.

[0078] “Homology” refers to sequence similarity or, interchangeably,sequence identity, between two or more polynucleotide sequences or twoor more polypeptide sequences.

[0079] The terms “percent identity” and “% identity,” as applied topolynucleotide sequences, refer to the percentage of residue matchesbetween at least two polynucleotide sequences aligned using astandardized algorithm. Such an algorithm may insert, in a standardizedand reproducible way, gaps in the sequences being compared in order tooptimize alignment between two sequences, and therefore achieve a moremeaningful comparison of the two sequences.

[0080] Percent identity between polynucleotide sequences may bedetermined using the default parameters of the CLUSTAL V algorithm asincorporated into the MEGAUGN version 3.12e sequence alignment program.This program is part of the LASERGENE software package, a suite ofmolecular biological analysis programs (DNASTAR, Madison Wis.). CLUSTALV is described in Higgins, D. G. and P. M. Sharp (1989) CABIOS 5:151-153and in Higgins, D. G. et al. (1992) CABIOS 8:189-191. For pairwisealignments of polynucleotide sequences, the default parameters are setas follows: Ktuple=2, gap penalty=5, window=4, and “diagonals saved”=4.The “weighted” residue weight table is selected as the default. Percentidentity is reported by CLUSTAL V as the “percent similarity” betweenaligned polynucleotide sequences.

[0081] Alternatively, a suite of commonly used and freely availablesequence comparison algorithms is provided by the National Center forBiotechnology Information (NCBI) Basic Local Alignment Search Tool(BLAST) (Altschul, S. F. et al. (1990) J. Mol. Biol. 215:403-410), whichis available from several sources, including the NCBI, Bethesda, Md.,and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLASTsoftware suite includes various sequence analysis programs including“blastn,” that is used to align a known polynucleotide sequence withother polynucleotide sequences from a variety of databases. Alsoavailable is a tool called “BLAST 2 Sequences” that is used for directpairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” canbe accessed and used interactively athttp://www.ncbi.nlm.nih.gov/gorf/b12.html. The “BLAST 2 Sequences” toolcan be used for both blastn and blastp (discussed below). BLAST programsare commonly used with gap and other parameters set to default settings.For example, to compare two nucleotide sequences, one may use blastnwith the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) set atdefault parameters. Such default parameters may be, for example:

[0082] Matrix: BLOSUM62

[0083] Reward for match: 1

[0084] Penalty for mismatch: −2

[0085] Open Gap: 5 and Extension Gap: 2 penalties

[0086] Gap x drop-off. 50

[0087] Expect: 10

[0088] Word Size: 11

[0089] Filter: on

[0090] Percent identity may be measured over the length of an entiredefined sequence, for example, as defined by a particular SEQ ID number,or may be measured over a shorter length, for example, over the lengthof a fragment taken from a larger, defined sequence, for instance, afragment of at least 20, at least 30, at least 40, at least 50, at least70, at least 100, or at least 200 contiguous nucleotides. Such lengthsare exemplary only, and it is understood that any fragment lengthsupported by the sequences shown herein, in the tables, figures, orSequence Listing, may be used to describe a length over which percentageidentity may be measured.

[0091] Nucleic acid sequences that do not show a high degree of identitymay nevertheless encode similar amino acid sequences due to thedegeneracy of the genetic code. It is understood that changes in anucleic acid sequence can be made using this degeneracy to producemultiple nucleic acid sequences that all encode substantially the sameprotein.

[0092] The phrases “percent identity” and “% identity,” as applied topolypeptide sequences, refer to the percentage of residue matchesbetween at least two polypeptide sequences aligned using a standardizedalgorithm. Methods of polypeptide sequence alignment are well-known.Some alignment methods take into account conservative amino acidsubstitutions. Such conservative substitutions, explained in more detailabove, generally preserve the charge and hydrophobicity at the site ofsubstitution, thus preserving the structure (and therefore function) ofthe polypeptide.

[0093] Percent identity between polypeptide sequences may be determinedusing the default parameters of the CLUSTAL V algorithm as incorporatedinto the MEGALIGN version 3.12e sequence alignment program (describedand referenced above). For pairwise alignments of polypeptide sequencesusing CLUSTAL V, the default parameters are set as follows: Ktuple=1,gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix isselected as the default residue weight table. As with polynucleotidealignments, the percent identity is reported by CLUSTAL V as the“percent similarity” between aligned polypeptide sequence pairs.

[0094] Alternatively the NCBI BLAST software suite maybe used. Forexample, for a pairwise comparison of two polypeptide sequences, one mayuse the “BLAST 2 Sequences” tool Version 2.0.12 (Apr. 21, 2000) withblastp set at default parameters. Such default parameters maybe, forexample:

[0095] Matrix: BLOSUM62

[0096] Open Gap: 11 and Extension Gap: 1 penalties

[0097] Gap x drop-off. 50

[0098] Expect: 10

[0099] Word Size: 3

[0100] Filter: on

[0101] Percent identity may be measured over the length of an entiredefined polypeptide sequence, for example, as defined by a particularSEQ ID number, or may be measured over a shorter length, for example,over the length of a fragment taken from a larger, defined polypeptidesequence, for instance, a fragment of at least 15, at least 20, at least30, at least 40, at least 50, at least 70 or at least 150 contiguousresidues. Such lengths are exemplary only, and it is understood that anyfragment length supported by the sequences shown herein, in the tables,figures or Sequence Listing, may be used to describe a length over whichpercentage identity may be measured.

[0102] “Human artificial chromosomes” (HACs) are linear microchromosomeswhich may contain DNA sequences of about 6 kb to 10 Mb in size and whichcontain all of the elements required for chromosome replication,segregation and maintenance.

[0103] The term “humanized antibody” refers to an antibody molecule inwhich the amino acid sequence in the non-antigen binding regions hasbeen altered so that the antibody more closely resembles a humanantibody, and still retains its original binding ability.

[0104] “Hybridization” refers to the process by which a polynucleotidestrand anneals with a complementary strand through base pairing underdefined hybridization conditions. Specific hybridization is anindication that two nucleic acid sequences share a high degree ofcomplementarity. Specific hybridization complexes form under permissiveannealing conditions and remain hybridized after the “washing” step(s).The washing step(s) is particularly important in determining thestringency of the hybridization process, with more stringent conditionsallowing less non-specific binding, i.e., binding between pairs ofnucleic acid strands that are not perfectly matched. Permissiveconditions for annealing of nucleic acid sequences are routinelydeterminable by one of ordinary skill in the art and may be consistentamong hybridization experiments, whereas wash conditions may be variedamong experiments to achieve the desired stringency, and thereforehybridization specificity. Permissive annealing conditions occur, forexample, at 68° C. in the presence of about 6×SSC, about 1% (w/v) SDS,and about 100 μg/ml sheared, denatured salmon sperm DNA.

[0105] Generally, stringency of hybridization is expressed, in part,with reference to the temperature under which the wash step is carriedout. Such wash temperatures are typically selected to be about 5° C. to20° C. lower than the thermal melting point (T_(m)) for the specificsequence at a defined ionic strength and pH. The T_(m) is thetemperature (under defined ionic strength and pH) at which 50% of thetarget sequence hybridizes to a perfectly matched probe. An equation forcalculating T_(m) and conditions for nucleic acid hybridization are wellknown and can be found in Sambrook, J. et al. (1989) Molecular Cloning:A Laboratory Manual, 2^(nd) ed., vol. 1-3, Cold Spring Harbor Press,Plainview N.Y.; specifically see volume 2, chapter 9.

[0106] High stringency conditions for hybridization betweenpolynucleotides of the present invention include wash conditions of 68°C. in the presence of about 0.2×SSC and about 0.1% SDS, for 1 hour.Alternatively, temperatures of about 65° C., 60° C., 55° C., or 42° C.may be used. SSC concentration may be varied from about 0.1 to 2×SSC,with SDS being present at about 0.1%. Typically, blocking reagents areused to block non-specific hybridization. Such blocking reagentsinclude, for instance, sheared and denatured salmon sperm DNA at about100-200 μg/ml. Organic solvent, such as formamide at a concentration ofabout 35-50% v/v, may also be used under particular circumstances, suchas for RNA:DNA hybridizations. Useful variations on these washconditions will be readily apparent to those of ordinary skill in theart. Hybridization, particularly under high stringency conditions, maybe suggestive of evolutionary similarity between the nucleotides. Suchsimilarity is strongly indicative of a similar role for the nucleotidesand their encoded polypeptides.

[0107] The term “hybridization complex” refers to a complex formedbetween two nucleic acid sequences by virtue of the formation ofhydrogen bonds between complementary bases. A hybridization complex maybe formed in solution (e.g., C₀ ^(t) or R₀ ^(t) analysis) or formedbetween one nucleic acid sequence present in solution and anothernucleic acid sequence immobilized on a solid support (e.g., paper,membranes, filters, chips, pins or glass slides, or any otherappropriate substrate to which cells or their nucleic acids have beenfixed).

[0108] The words “insertion” and “addition” refer to changes in an aminoacid or nucleotide sequence resulting in the addition of one or moreamino acid residues or nucleotides, respectively.

[0109] “Immune response” can refer to conditions associated withinflammation, trauma, immune disorders, or infectious or geneticdisease, etc. These conditions can be characterized by expression ofvarious factors, e.g., cytokines, chemokines, and other signalingmolecules, which may affect cellular and systemic defense systems.

[0110] An “immunogenic fragment” is a polypeptide or oligopeptidefragment of GCREC which is capable of eliciting an immune response whenintroduced into a living organism, for example, a mammal. The term“immunogenic fragment” also includes any polypeptide or oligopeptidefragment of GCREC which is useful in any of the antibody productionmethods disclosed herein or known in the art.

[0111] The term “microarray” refers to an arrangement of a plurality ofpolynucleotides, polypeptides, or other chemical compounds on asubstrate.

[0112] The terms “element” and “array element” refer to apolynucleotide, polypeptide, or other chemical compound having a uniqueand defined position on a microarray.

[0113] The term “modulate” refers to a change in the activity of GCREC.For example, modulation may cause an increase or a decrease in proteinactivity, binding characteristics, or any other biological, functional,or immunological properties of GCREC.

[0114] The phrases “nucleic acid” and “nucleic acid sequence” refer to anucleotide, oligonucleotide, polynucleotide, or any fragment thereof.These phrases also refer to DNA or RNA of genomic or synthetic originwhich may be single-stranded or double-stranded and may represent thesense or the antisense strand, to peptide nucleic acid (PNA), or to anyDNA-like or RNA-like material.

[0115] “Operably linked” refers to the situation in which a firstnucleic acid sequence is placed in a functional relationship with asecond nucleic acid sequence. For instance, a promoter is operablylinked to a coding sequence if the promoter affects the transcription orexpression of the coding sequence. Operably linked DNA sequences may bein close proximity or contiguous and, where necessary to join twoprotein coding regions, in the same reading frame.

[0116] “Peptide nucleic acid” (PNA) refers to an antisense molecule oranti-gene agent which comprises an oligonucleotide of at least about 5nucleotides in length linked to a peptide backbone of amino acidresidues ending in lysine. The terminal lysine confers solubility to thecomposition. PNAs preferentially bind complementary single stranded DNAor RNA and stop transcript elongation, and may be pegylated to extendtheir lifespan in the cell.

[0117] “Post-translational modification” of an GCREC may involvelipidation, glycosylation, phosphorylation, acetylation, racemization,proteolytic cleavage, and other modifications known in the art. Theseprocesses may occur synthetically or biochemically. Biochemicalmodifications will vary by cell type depending on the enzymatic milieuof GCREC.

[0118] “Probe” refers to nucleic acid sequences encoding GCREC, theircomplements, or fragments thereof, which are used to detect identical,allelic or related nucleic acid sequences. Probes are isolatedoligonucleotides or polynucleotides attached to a detectable label orreporter molecule. Typical labels include radioactive isotopes, ligands,chemiluminescent agents, and enzymes. “Primers” are short nucleic acids,usually DNA oligonucleotides, which may be annealed to a targetpolynucleotide by complementary base-pairing. The primer may then beextended along the target DNA strand by a DNA polymerase enzyme. Primerpairs can be used for amplification (and identification) of a nucleicacid sequence, e.g., by the polymerase chain reaction (PCR).

[0119] Probes and primers as used in the present invention typicallycomprise at least 15 contiguous nucleotides of a known sequence. Inorder to enhance specificity, longer probes and primers may also beemployed, such as probes and primers that comprise at least 20, 25, 30,40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides ofthe disclosed nucleic acid sequences. Probes and primers may beconsiderably longer than these examples, and it is understood that anylength supported by the specification, including the tables, figures,and Sequence Listing, may be used.

[0120] Methods for preparing and using probes and primers are describedin the references, for example Sambrook, J. et al. (1989) MolecularCloning: A Laboratory Manual, 2^(nd) ed., vol. 1-3, Cold Spring HarborPress, Plainview N.Y.; Ausubel, F. M. et al. (1987) Current Protocols inMolecular Biology, Greene Publ. Assoc. & Wiley-Intersciences, New YorkN.Y.; Innis, M. et al. (1990) PCR Protocols. A Guide to Methods andApplications, Academic Press, San Diego Calif. PCR primer pairs can bederived from a known sequence, for example, by using computer programsintended for that purpose such as Primer (Version 0.5, 1991, WhiteheadInstitute for Biomedical Research, Cambridge Mass.).

[0121] Oligonucleotides for use as primers are selected using softwareknown in the art for such purpose. For example, OLIGO 4.06 software isuseful for the selection of PCR primer pairs of up to 100 nucleotideseach, and for the analysis of oligonucleotides and largerpolynucleotides of up to 5,000 nucleotides from an input polynucleotidesequence of up to 32 kilobases. Similar primer selection programs haveincorporated additional features for expanded capabilities. For example,the PrimOU primer selection program (available to the public from theGenome Center at University of Texas South West Medical Center, DallasTex.) is capable of choosing specific primers from megabase sequencesand is thus useful for designing primers on a genome-wide scope. ThePrimer3 primer selection program (available to the public from theWhitehead Institute/MIT Center for Genome Research, Cambridge Mass.)allows the user to input a “rispriming library,” in which sequences toavoid as primer binding sites are user-specified. Primer3 is useful, inparticular, for the selection of oligonucleotides for microarrays. (Thesource code for the latter two primer selection programs may also beobtained from their respective sources and modified to meet the user'sspecific needs.) The PrimeGen program (available to the public from theUK Human Genome Mapping Project Resource Centre, Cambridge UK) designsprimers based on multiple sequence alignments, thereby allowingselection of primers that hybridize to either the most conserved orleast conserved regions of aligned nucleic acid sequences. Hence, thisprogram is useful for identification of both unique and conservedoligonucleotides and polynucleotide fragments. The oligonucleotides andpolynucleotide fragments identified by any of the above selectionmethods are useful in hybridization technologies, for example, as PCR orsequencing primers, microarray elements, or specific probes to identifyfully or partially complementary polynucleotides in a sample of nucleicacids. Methods of oligonucleotide selection are not limited to thosedescribed above.

[0122] A “recombinant nucleic acid” is a sequence that is not naturallyoccurring or has a sequence that is made by an artificial combination oftwo or more otherwise separated segments of sequence. This artificialcombination is often accomplished by chemical synthesis or, morecommonly, by the artificial manipulation of isolated segments of nucleicacids, e.g., by genetic engineering techniques such as those describedin Sambrook, supra. The term recombinant includes nucleic acids thathave been altered solely by addition, substitution, or deletion of aportion of the nucleic acid. Frequently, a recombinant nucleic acid mayinclude a nucleic acid sequence operably linked to a promoter sequence.Such a recombinant nucleic acid may be part of a vector that is used,for example, to transform a cell.

[0123] Alternatively, such recombinant nucleic acids may be part of aviral vector, e.g., based on a vaccima virus, that could be use tovaccinate a mammal wherein the recombinant nucleic acid is expressed,inducing a protective immunological response in the mammal.

[0124] A “regulatory element” refers to a nucleic acid sequence usuallyderived from untranslated regions of a gene and includes enhancers,promoters, introns, and 5′ and 3′ untranslated regions (UTRs).Regulatory elements interact with host or viral proteins which controltranscription, translation, or RNA stability.

[0125] “Reporter molecules” are chemical or biochemical moieties usedfor labeling a nucleic acid, amino acid, or antibody. Reporter moleculesinclude radionuclides; enzymes; fluorescent, chemiluminescent, orchromogenic agents; substrates; cofactors; inhibitors; magneticparticles; and other moieties known in the art.

[0126] An “RNA equivalent,” in reference to a DNA sequence, is composedof the same linear sequence of nucleotides as the reference DNA sequencewith the exception that all occurrences of the nitrogenous base thymineare replaced with uracil, and the sugar backbone is composed of riboseinstead of deoxyribose.

[0127] The term “sample” is used in its broadest sense. A samplesuspected of containing GCREC, nucleic acids encoding GCREC, orfragments thereof may comprise a bodily fluid; an extract from a cell,chromosome, organelle, or membrane isolated from a cell; a cell; genomicDNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; atissue print; etc.

[0128] The terms “specific binding” and “specifically binding” refer tothat interaction between a protein or peptide and an agonist, anantibody, an antagonist, a small molecule, or any natural or syntheticbinding composition. The interaction is dependent upon the presence of aparticular structure of the protein, e.g., the antigenic determinant orepitope, recognized by the binding molecule. For example, if an antibodyis specific for epitope “A,” the presence of a polypeptide comprisingthe epitope A, or the presence of free unlabeled A, in a reactioncontaining free labeled A and the antibody will reduce the amount oflabeled A that binds to the antibody.

[0129] The term “substantially purified” refers to nucleic acid or aminoacid sequences that are removed from their natural environment and areisolated or separated, and are at least 60% free, preferably at least75% free, and most preferably at least 90% free from other componentswith which they are naturally associated.

[0130] A “substitution” refers to the replacement of one or more aminoacid residues or nucleotides by different amino acid residues ornucleotides, respectively.

[0131] “Substrate” refers to any suitable rigid or semi-rigid supportincluding membranes, filters, chips, slides, wafers, fibers, magnetic ornonmagnetic beads, gels, tubing, plates, polymers, microparticles andcapillaries. The substrate can have a variety of surface forms, such aswells, trenches, pins, channels and pores, to which polynucleotides orpolypeptides are bound.

[0132] A “transcript image” or “expression profile” refers to thecollective pattern of gene expression by a particular cell type ortissue under given conditions at a given time.

[0133] “Transformation” describes a process by which exogenous DNA isintroduced into a recipient cell. Transformation may occur under naturalor artificial conditions according to various methods well known in theart, and may rely on any known method for the insertion of foreignnucleic acid sequences into a prokaryotic or eukaryotic host cell. Themethod for transformation is selected based on the type of host cellbeing transformed and may include, but is not limited to, bacteriophageor viral infection, electroporation, heat shock, lipofection, andparticle bombardment. The term “transformed cells” includes stablytransformed cells in which the inserted DNA is capable of replicationeither as an autonomously replicating plasmid or as part of the hostchromosome, as well as transiently transformed cells which express theinserted DNA or RNA for limited periods of time.

[0134] A “transgenic organism,” as used herein, is any organism,including but not limited to animals and plants, in which one or more ofthe cells of the organism contains heterologous nucleic acid introducedby way of human intervention, such as by transgenic techniques wellknown in the art. The nucleic acid is introduced into the cell, directlyor indirectly by introduction into a precursor of the cell, by way ofdeliberate genetic manipulation, such as by microinjection or byinfection with a recombinant virus. In one alternative, the nucleic acidcan be introduced by infection with a recombinant viral vector, such asa lentiviral vector (Lois, C. et al. (2002) Science 295:868-872). Theterm genetic manipulation does not include classical cross-breeding, orin vitro fertilization, but rather is directed to the introduction of arecombinant DNA molecule. The transgenic organisms contemplated inaccordance with the present invention include bacteria, cyanobacteria,fungi, plants and animals. The isolated DNA of the present invention canbe introduced into the host by methods known in the art, for exampleinfection, transfection, transformation or transconjugation. Techniquesfor transferring the DNA of the present invention into such organismsare widely known and provided in references such as Sambrook et al.(1989), supra.

[0135] A “variant” of a particular nucleic acid sequence is defined as anucleic acid sequence having at least 40% sequence identity to theparticular nucleic acid sequence over a certain length of one of thenucleic acid sequences using blastn with the “BLAST 2 Sequences” toolVersion 2.0.9 (May 7, 1999) set at default parameters. Such a pair ofnucleic acids may show, for example, at least 50%, at least 60%, atleast 70%, at least 80%, at least 85%, at least 90%, at least 91%, atleast 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99% or greater sequence identityover a certain defined length. A variant may be described as, forexample, an “allelic” (as defined above), “splice,” “species,” or“polymorphic” variant. A splice variant may have significant identity toa reference molecule, but will generally have a greater or lesser numberof polynucleotides due to alternate splicing of exons during mRNAprocessing. The corresponding polypeptide may possess additionalfunctional domains or lack domains that are present in the referencemolecule. Species variants are polynucleotide sequences that vary fromone species to another. The resulting polypeptides will generally havesignificant amino acid identity relative to each other. A polymorphicvariant is a variation in the polynucleotide sequence of a particulargene between individuals of a given species. Polymorphic variants alsomay encompass “single nucleotide polymorphisms” (SNPs) in which thepolynucleotide sequence varies by one nucleotide base. The presence ofSNPs may be indicative of, for example, a certain population, a diseasestate, or a propensity for a disease state.

[0136] A “variant” of a particular polypeptide sequence is defined as apolypeptide sequence having at least 40% sequence identity to theparticular polypeptide sequence over a certain length of one of thepolypeptide sequences using blastp with the “BLAST 2 Sequences” toolVersion 2.0.9 (May 7, 1999) set at default parameters. Such a pair ofpolypeptides may show, for example, at least 50%, at least 60%, at least70%, at least 80%, at least 90%, at least 91%, at least 92%, at least93%, at least 94%, at least 95%, at least 96%, at least 97%, at least98%, or at least 99% or greater sequence identity over a certain definedlength of one of the polypeptides.

THE INVENTION

[0137] The invention is based on the discovery of new human G-proteincoupled receptors (GCREC), the polynucleotides encoding GCREC, and theuse of these compositions for the diagnosis, treatment, or prevention ofcell proliferative, neurological, cardiovascular, gastrointestinal,autoimmune/inflammatory, and metabolic disorders, and viral infections.

[0138] Table 1 summarizes the nomenclature for the full lengthpolynucleotide and polypeptide sequences of the invention. Eachpolynucleotide and its corresponding polypeptide are correlated to asingle Incyte project identification number (Incyte Project ID). Eachpolypeptide sequence is denoted by both a polypeptide sequenceidentification number (Polypeptide SEQ ID NO:) and an Incyte polypeptidesequence number (Incyte Polypeptide ID) as shown. Each polynucleotidesequence is denoted by both a polynucleotide sequence identificationnumber (Polynucleotide SEQ ID NO:) and an Incyte polynucleotideconsensus sequence number (Incyte Polynucleotide ID) as shown.

[0139] Table 2 shows sequences with homology to the polypeptides of theinvention as identified by BLAST analysis against the GenBank protein(genpept) database. Columns 1 and 2 show the polypeptide sequenceidentification number (Polypeptide SEQ ID NO:) and the correspondingIncyte polypeptide sequence number (Incyte Polypeptide ID) forpolypeptides of the invention. Column 3 shows the GenBank identificationnumber (GenBank ID NO:) of the nearest GenBank homolog. Column 4 showsthe probability scores for the matches between each polypeptide and itshomolog(s). Column 5 shows the annotation of the GenBank homolog(s)along with relevant citations where applicable, all of which areexpressly incorporated by reference herein.

[0140] Table 3 shows various structural features of the polypeptides ofthe invention. Columns 1 and 2 show the polypeptide sequenceidentification number (SEQ ID NO:) and the corresponding Incytepolypeptide sequence number (Incyte Polypeptide ID) for each polypeptideof the invention. Column 3 shows the number of amino acid residues ineach polypeptide. Column 4 shows potential phosphorylation sites, andcolumn 5 shows potential glycosylation sites, as determined by theMOTIFS program of the GCG sequence analysis software package (GeneticsComputer Group, Madison Wis.). Column 6 shows amino acid residuescomprising signature sequences, domains, and motifs. Column 7 showsanalytical methods for protein structure/function analysis and in somecases, searchable databases to which the analytical methods wereapplied.

[0141] Together, Tables 2 and 3 summarize the properties of polypeptidesof the invention, and these properties establish that the claimedpolypeptides are G-protein coupled receptors. For example, SEQ ID NO:1is 80% identical, from residue V24 to residue L287, to rat odorantreceptor (GenBank ID g10644517) as determined by the Basic LocalAlignment Search Tool (BLAST). (See Table 2.) The BLAST probabilityscore is 1.0e-110, which indicates the probability of obtaining theobserved polypeptide sequence alignment by chance. SEQ ID NO:1 alsocontains a 7 transmembrane receptor (rhodopsin family) domain asdetermined by searching for statistically significant matches in thehidden Markov model (HMM)-based PFAM database of conserved proteinfamily domains. (See Table 3.) Data from BLIMPS analysis provide furthercorroborative evidence that SEQ ID NO:1 is an odorant receptor.

[0142] As another example, SEQ ID NO:39 is 59% identical, from residueM1 to residue V305, to a Mus musculus olfactory receptor (GenBank IDg200154) as determined by the Basic Local Alignment Search Tool (BLAST).The BLAST probability score is 1.6e-98, which indicates the probabilityof obtaining the observed polypeptide sequence alignment by chance. SEQID NO:39 also contains a 7-transmembrane receptor rhodopsin familydomain as determined by searching for statistically significant matchesin the hidden Markov model (HMM)-based PFAM database of conservedprotein family domains. (See Table 3.) Data from BUMPS, MOTIFS, andPROFILESCAN analyses provide further corroborative evidence that SEQ IDNO:39 is a G-protein coupled olfactory receptor.

[0143] In an alternative example, SEQ ID NO:51 is 67% identical, fromresidue M1 to residue I311, to a human olfactory receptor, OR18 (GenBankID g4159886) as determined by the Basic Local Alignment Search Tool(BLAST). The BLAST probability score is 5.6e-112, which indicates theprobability of obtaining the observed polypeptide sequence alignment bychance. SEQ ID NO:51 also contains a 7 transmembrane receptor (rhodopsinfamily) domain as determined by searching for statistically significantmatches in the hidden Markov model (HMM)-based PFAM database ofconserved protein family domains. (See Table 3.) Data from BLIMPS,MOTIFS, and PROFILESCAN analyses provide further corroborative evidencethat SEQ ID NO:51 is an olfactory receptor.

[0144] In an alternative example, SEQ ID NO:60 is 53% identical, fromresidue M1 to residue R308, to chicken olfactory receptor 4 (GenBank IDg1246534) as determined by the Basic Local Alignment Search Tool(BLAST). (See Table 2.) The BLAST probability score is 2.1e-89, whichindicates the probability of obtaining the observed polypeptide sequencealignment by chance. SEQ ID NO:60 also contains a 7 transmembranereceptor (rhodopsin family) domain as determined by searching forstatistically significant matches in the hidden Markov model (HMM)-basedPFAM database of conserved protein family domains. (See Table 3.) Datafrom BLIMPS, MOTIFS, and PROFILESCAN analyses provide furthercorroborative evidence that SEQ ID NO:60 is an olfactory receptor.

[0145] SEQ ID NO:2-38, SEQ ID NO:40-50, SEQ ID NO:52-59 and SEQ IDNO:61-73 were analyzed and annotated in a similar manner. The algorithmsand parameters for the analysis of SEQ ID NO:1-73 are described in Table7.

[0146] As shown in Table 4, the full length polynucleotide sequences ofthe present invention were assembled using cDNA sequences or coding(exon) sequences derived from genomic DNA, or any combination of thesetwo types of sequences. Column 1 lists the polynucleotide sequenceidentification number (Polynucleotide SEQ ID NO:), the correspondingIncyte polynucleotide consensus sequence number (Incyte ID) for eachpolynucleotide of the invention, and the length of each polynucleotidesequence in basepairs. Column 2 shows the nucleotide start (5′) and stop(3′) positions of the cDNA and/or genomic sequences used to assemble thefull length polynucleotide sequences of the invention, and of fragmentsof the polynucleotide sequences which are useful, for example, inhybridization or amplification technologies that identify SEQ IDNO:74-146 or that distinguish between SEQ ID NO:74-146 and relatedpolynucleotide sequences.

[0147] The polynucleotide fragments described in Column 2 of Table 4 mayrefer specifically, for example, to Incyte cDNAs derived fromtissue-specific cDNA libraries or from pooled cDNA libraries.Alternatively, the polynucleotide fragments described in column 2 mayrefer to GenBank cDNAs or ESTs which contributed to the assembly of thefull length polynucleotide sequences. In addition, the polynucleotidefragments described in column 2 may identify sequences derived from theENSEMBL (The Sanger Centre, Cambridge, UK) database (ie., thosesequences including the designation “ENST”). Alternatively, thepolynucleotide fragments described in column 2 may be derived from theNCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequencesincluding the designation “NM” or “NT”) or the NCBI RefSeq ProteinSequence Records (i.e., those sequences including the designation “NP”).Alternatively, the polynucleotide fragments described in column 2 mayrefer to assemblages of both cDNA and Genscan-predicted exons broughttogether by an “exon stitching” algorithm. For example, a polynucleotidesequence identified as FL_XXXXXX_N₁_N₂_YYYYY_N_(3—)N₄ represents a“stitched” sequence in which XXXXXX is the identification number of thecluster of sequences to which the algorithm was applied, and YYYYY isthe number of the prediction generated by the algorithm, andN_(1, 2, 3 . . .) , if present, represent specific exons that may havebeen manually edited during analysis (See Example V). Alternatively, thepolynucleotide fragments in column 2 may refer to assemblages of exonsbrought together by an “exon-stretching” algorithm. For example, apolynucleotide sequence identified as FLXXXXXX_gAAAAA_gBBBBB_(—)1_N is a“stretched” sequence, with XXXXXX being the Incyte projectidentification number, gAAAAA being the GenBank identification number ofthe human genomic sequence to which the “exon-stretching” algorithm wasapplied, GBBBBB being the GenBank identification number or NCBI RefSeqidentification number of the nearest GenBank protein homolog, and Nreferring to specific exons (See Example V). In instances where a RefSeqsequence was used as a protein homolog for the “exon-stretching”algorithm, a RefSeq identifier (denoted by “NM,” “NP,” or “NT”) may beused in place of the GenBank identifier (i.e., gBBBBB).

[0148] Alternatively, a prefix identifies component sequences that werehand-edited, predicted from genomic DNA sequences, or derived from acombination of sequence analysis methods. The following Table listsexamples of component sequence prefixes and corresponding sequenceanalysis methods associated with the prefixes (see Example IV andExample V). Prefix Type of analysis and/or examples of programs GNN,Exon prediction from genomic sequences using, for example, GFG, GENSCAN(Stanford University, CA, USA) or FGENES ENST (Computer Genomics Group,The Sanger Centre, Cambridge, UK) GBI Hand-edited analysis of genomicsequences. FL Stitched or stretched genomic sequences (see Example V).INCY Full length transcript and exon prediction from mapping of ESTsequences to the genome. Genomic location and EST composition data arecombined to predict the exons and resulting transcript.

[0149] In some cases, Incyte cDNA coverage redundant with the sequencecoverage shown in Table 4 was obtained to confirm the final consensuspolynucleotide sequence, but the relevant Incyte cDNA identificationnumbers are not shown.

[0150] Table 5 shows the representative cDNA libraries for those fulllength polynucleotide sequences which were assembled using Incyte cDNAsequences. The representative cDNA library is the Incyte cDNA librarywhich is most frequently represented by the Incyte cDNA sequences whichwere used to assemble and confirm the above polynucleotide sequences.The tissues and vectors which were used to construct the cDNA librariesshown in Table 5 are described in Table 6.

[0151] The invention also encompasses GCREC variants. A preferred GCRECvariant is one which has at least about 80%, or alternatively at leastabout 90%, or even at least about 95% amino acid sequence identity tothe GCREC amino acid sequence, and which contains at least onefunctional or structural characteristic of GCREC.

[0152] The invention also encompasses polynucleotides which encodeGCREC. In a particular embodiment, the invention encompasses apolynucleotide sequence comprising a sequence selected from the groupconsisting of SEQ ID NO:74-146, which encodes GCREC. The polynucleotidesequences of SEQ ID NO:74-146, as presented in the Sequence Listing,embrace the equivalent RNA sequences, wherein occurrences of thenitrogenous base thymine are replaced with uracil, and the sugarbackbone is composed of ribose instead of deoxyribose.

[0153] The invention also encompasses a variant of a polynucleotidesequence encoding GCREC. In particular, such a variant polynucleotidesequence will have at least about 70%, or alternatively at least about85%, or even at least about 95% polynucleotide sequence identity to thepolynucleotide sequence encoding GCREC. A particular aspect of theinvention encompasses a variant of a polynucleotide sequence comprisinga sequence selected from the group consisting of SEQ ID NO:74-146 whichhas at least about 70%, or alternatively at least about 85%, or even atleast about 95% polynucleotide sequence identity to a nucleic acidsequence selected from the group consisting of SEQ ID NO:74-146. Any oneof the polynucleotide variants described above can encode an amino acidsequence which contains at least one functional or structuralcharacteristic of GCREC.

[0154] In addition, or in the alternative, a polynucleotide variant ofthe invention is a splice variant of a polynucleotide sequence encodingGCREC. A splice variant may have portions which have significantsequence identity to the polynucleotide sequence encoding GCREC, butwill generally have a greater or lesser number of polynucleotides due toadditions or deletions of blocks of sequence arising from alternatesplicing of exons during mRNA processing. A splice variant may have lessthan about 70%, or alternatively less than about 60%, or alternativelyless than about 50% polynucleotide sequence identity to thepolynucleotide sequence encoding GCREC over its entire length; however,portions of the splice variant will have at least about 70%, oralternatively at least about 85%, or alternatively at least about 95%,or alternatively 100% polynucleotide sequence identity to portions ofthe polynucleotide sequence encoding GCREC. Any one of the splicevariants described above can encode an amino acid sequence whichcontains at least one functional or structural characteristic of GCREC.

[0155] It will be appreciated by those skilled in the art that as aresult of the degeneracy of the genetic code, a multitude ofpolynucleotide sequences encoding GCREC, some bearing minimal similarityto the polynucleotide sequences of any known and naturally occurringgene, may be produced. Thus, the invention contemplates each and everypossible variation of polynucleotide sequence that could be made byselecting combinations based on possible codon choices. Thesecombinations are made in accordance with the standard triplet geneticcode as applied to the polynucleotide sequence of naturally occurringGCREC, and all such variations are to be considered as beingspecifically disclosed.

[0156] Although nucleotide sequences which encode GCREC and its variantsare generally capable of hybridizing to the nucleotide sequence of thenaturally occurring GCREC under appropriately selected conditions ofstringency, it may be advantageous to produce nucleotide sequencesencoding GCREC or its derivatives possessing a substantially differentcodon usage, e.g., inclusion of non-naturally occurring codons. Codonsmay be selected to increase the rate at which expression of the peptideoccurs in a particular prokaryotic or eukaryotic host in accordance withthe frequency with which particular codons are utilized by the host.Other reasons for substantially altering the nucleotide sequenceencoding GCREC and its derivatives without altering the encoded aminoacid sequences include the production of RNA transcripts having moredesirable properties, such as a greater half-life, than transcriptsproduced from the naturally occurring sequence.

[0157] The invention also encompasses production of DNA sequences whichencode GCREC and GCREC derivatives, or fragments thereof, entirely bysynthetic chemistry. After production, the synthetic sequence may beinserted into any of the many available expression vectors and cellsystems using reagents well known in the art. Moreover, syntheticchemistry may be used to introduce mutations into a sequence encodingGCREC or any fragment thereof.

[0158] Also encompassed by the invention are polynucleotide sequencesthat are capable of hybridizing to the claimed polynucleotide sequences,and, in particular, to those shown in SEQ ID NO:74-146 and fragmentsthereof under various conditions of stringency. (See, e.g., Wahl, G. M.and S. L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A. R.(1987) Methods Enzymol. 152:507-511.) Hybridization conditions,including annealing and wash conditions, are described in “Definitions.”

[0159] Methods for DNA sequencing are well known in the art and may beused to practice any of the embodiments of the invention. The methodsmay employ such enzymes as the Klenow fragment of DNA polymerase I,SEQUENASE (US Biochemical, Cleveland Ohio), Taq polymerase (AppliedBiosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech,Piscataway N.J.), or combinations of polymerases and proofreadingexonucleases such as those found in the ELONGASE amplification system(Life Technologies, Gaithersburg Md.). Preferably, sequence preparationis automated with machines such as the MICROLAB 2200 liquid transfersystem (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research,Watertown Mass.) and ABI CATALYST 800 thermal cycler (AppliedBiosystems). Sequencing is then carried out using either the ABI 373 or377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNAsequencing system (Molecular Dynamics, Sunnyvale Calif.), or othersystems known in the arts The resulting sequences are analyzed using avariety of algorithms which are well known in the art. (See, e.g.,Ausubel, F. M. (1997) Short Protocols in Molecular Biology, John Wiley &Sons, New York N.Y., unit 7.7; Meyers, R. A. (1995) Molecular Biologyand Biotechnology, Wiley VCH, New York N.Y., pp. 856-853.)

[0160] The nucleic acid sequences encoding GCREC may be extendedutilizing a partial nucleotide sequence and employing various PCR-basedmethods known in the art to detect upstream sequences, such as promotersand regulatory elements. For example, one method which may be employed,restriction-site PCR, uses universal and nested primers to amplifyunknown sequence from genomic DNA within a cloning vector. (See, e.g.,Sarkar, G. (1993) PCR Methods Applic. 2:318-322.) Another method,inverse PCR, uses primers that extend in divergent directions to amplifyunknown sequence from a circularized template. The template is derivedfrom restriction fragments comprising a known genomic locus andsurrounding sequences. (See, e.g., Triglia, T. et al. (1988) NucleicAcids Res. 16:8186.) A third method, capture PCR, involves PCRamplification of DNA fragments adjacent to known sequences in human andyeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al.(1991) PCR Methods Applic. 1:111-119.) In this method, multiplerestriction enzyme digestions and ligations may be used to insert anengineered double-stranded sequence into a region of unknown sequencebefore performing PCR. Other methods which may be used to retrieveunknown sequences are known in the art (See, e.g., Parker, J. D. et al.(1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR,nested primers, and PROMOTERFINDER libraries (Clontech, Palo AltoCalif.) to walk genomic DNA. This procedure avoids the need to screenlibraries and is useful in finding intron/exon junctions. For allPCR-based methods, primers may be designed using commercially availablesoftware, such as OLIGO 4.06 primer analysis software (NationalBiosciences, Plymouth Minn.) or another appropriate program, to be about22 to 30 nucleotides in length, to have a GC content of about 50% ormore, and to anneal to the template at temperatures of about 68° C. to72° C.

[0161] When screening for full length cDNAs, it is preferable to uselibraries that have been size-selected to include larger cDNAs. Inaddition, random-primed libraries, which often include sequencescontaining the 5′ regions of genes, are preferable for situations inwhich an oligo d(T) library does not yield a full-length cDNA. Genomiclibraries may be useful for extension of sequence into 5′non-transcribed regulatory regions.

[0162] Capillary electrophoresis systems which are commerciallyavailable may be used to analyze the size or confirm the nucleotidesequence of sequencing or PCR products. In particular, capillarysequencing may employ flowable polymers for electrophoretic separation,four different nucleotide-specific, laser-stimulated fluorescent dyes,and a charge coupled device camera for detection of the emittedwavelengths. Output/light intensity may be converted to electricalsignal using appropriate software (e.g., GENOTYPER and SEQUENCENAVIGATOR, Applied Biosystems), and the entire process from loading ofsamples to computer analysis and electronic data display may be computercontrolled. Capillary electrophoresis is especially preferable forsequencing small DNA fragments which may be present in limited amountsin a particular sample.

[0163] In another embodiment of the invention, polynucleotide sequencesor fragments thereof which encode GCREC may be cloned in recombinant DNAmolecules that direct expression of GCREC, or fragments or functionalequivalents thereof, in appropriate host cells. Due to the inherentdegeneracy of the genetic code, other DNA sequences which encodesubstantially the same or a functionally equivalent amino acid sequencemay be produced and used to express GCREC.

[0164] The nucleotide sequences of the present invention can beengineered using methods generally known in the art in order to alterGCREC-encoding sequences for a variety of purposes including, but notlimited to, modification of the cloning, processing, and/or expressionof the gene product. DNA shuffling by random fragmentation and PCRreassembly of gene fragments and synthetic oligonucleotides may be usedto engineer the nucleotide sequences. For example,oligonucleotide-mediated site-directed mutagenesis may be used tointroduce mutations that create new restriction sites, alterglycosylation patterns, change codon preference, produce splicevariants, and so forth.

[0165] The nucleotides of the present invention may be subjected to DNAshuffling techniques such as MOLECULARBREEDING (Maxygen Inc., SantaClara Calif.; described in U.S. Pat. No. 5,837,458; Chang, C.-C. et al.(1999) Nat. Biotechnol. 17:793-797; Christians, F. C. et al. (1999) Nat.Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol.14:315-319) to alter or improve the biological properties of GCREC, suchas its biological or enzymatic activity or its ability to bind to othermolecules or compounds. DNA shuffling is a process by which a library ofgene variants is produced using PCR-mediated recombination of genefragments. The library is then subjected to selection or screeningprocedures that identify those gene variants with the desiredproperties. These preferred variants may then be pooled and furthersubjected to recursive rounds of DNA shuffling and selection/screening.Thus, genetic diversity is created through “artificial” breeding andrapid molecular evolution. For example, fragments of a single genecontaining random point mutations may be recombined, screened, and thenreshuffled until the desired properties are optimized. Alternatively,fragments of a given gene may be recombined with fragments of homologousgenes in the same gene family, either from the same or differentspecies, thereby maximizing the genetic diversity of multiple naturallyoccurring genes in a directed and controllable manner.

[0166] In another embodiment, sequences encoding GCREC may besynthesized, in whole or in part, using chemical methods well known inthe art. (See, e.g., Caruthers, M. H. et al. (1980) Nucleic Acids Symp.Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser.7:225-232.) Alternatively, GCREC itself or a fragment thereof may besynthesized using chemical methods. For example, peptide synthesis canbe performed using various solution-phase or solid-phase techniques.(See, e.g., Creighton, T. (1984) Proteins, Structures and MolecularProperties, W H Freeman, New York N.Y., pp. 55-60; and Roberge, J. Y. etal. (1995) Science 269:202-204.) Automated synthesis maybe achievedusing the ABI 431A peptide synthesizer (Applied Biosystems).Additionally, the amino acid sequence of GCREC, or any part thereof, maybe altered during direct synthesis and/or combined with sequences fromother proteins, or any part thereof, to produce a variant polypeptide ora polypeptide having a sequence of a naturally occurring polypeptide.

[0167] The peptide may be substantially purified by preparative highperformance liquid chromatography. (See, e.g., Chiez, R. M. and F. Z.Regnier (1990) Methods Enzymol. 182:392-421.) The composition of thesynthetic peptides may be confirmed by amino acid analysis or bysequencing. (See, e.g., Creighton, surra, pp. 28-53.)

[0168] In order to express a biologically active GCREC, the nucleotidesequences encoding GCREC or derivatives thereof may be inserted into anappropriate expression vector, i.e., a vector which contains thenecessary elements for transcriptional and translational control of theinserted coding sequence in a suitable host. These elements includeregulatory sequences, such as enhancers, constitutive and induciblepromoters, and 5′ and 3′untranslated regions in the vector and inpolynucleotide sequences encoding GCREC. Such elements may vary in theirstrength and specificity. Specific initiation signals may also be usedto achieve more efficient translation of sequences encoding GCREC. Suchsignals include the ATG initiation codon and adjacent sequences, e.g.the Kozak sequence. In cases where sequences encoding GCREC and itsinitiation codon and upstream regulatory sequences are inserted into theappropriate expression vector, no additional transcriptional ortranslational control signals may be needed. However, in cases whereonly coding sequence, or a fragment thereof, is inserted, exogenoustranslational control signals including an in-frame ATG initiation codonshould be provided by the vector. Exogenous translational elements andinitiation codons may be of various origins, both natural and synthetic.The efficiency of expression may be enhanced by the inclusion ofenhancers appropriate for the particular host cell system used. (See,e.g., Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162.)

[0169] Methods which are well known to those skilled in the art may beused to construct expression vectors containing sequences encoding GCRECand appropriate transcriptional and translational control elements.These methods include in vitro recombinant DNA techniques, synthetictechniques, and in vivo genetic recombination. (See, e.g., Sambrook, J.et al. (1989) Molecular Cloning, A Laboratory Manual, Cold Spring HarborPress, Plainview N.Y., ch. 4, 8, and 16-17; Ausubel, F. M. et al. (1995)Current Protocols in Molecular Biology, John Wiley & Sons, New YorkN.Y., ch. 9, 13, and 16.)

[0170] A variety of expression vector/host systems may be utilized tocontain and express sequences encoding GCREC. These include, but are notlimited to, microorganisms such as bacteria transformed with recombinantbacteriophage, plasmid, or cosmid DNA expression vectors; yeasttransformed with yeast expression vectors; insect cell systems infectedwith viral expression vectors (e.g., baculovirus); plant cell systemstransformed with viral expression vectors (e.g., cauliflower mosaicvirus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expressionvectors (e.g., Ti or pBR322 plasmids); or animal cell systems. (See,e.g., Sambrook, supra; Ausubel, supra; Van Heeke, G. and S. M. Schuster(1989) J. Biol. Chem. 264:5503-5509; Engelhard, E. K. et al. (1994)Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum.Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311; TheMcGraw Hill Yearbook of Science and Technology (1992) McGraw Hill, NewYork N.Y., pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad.Sci. USA 81:3655-3659; and Harrington, J. J. et al. (1997) Nat. Genet.15:345-355.) Expression vectors derived from retroviruses, adenoviruses,or herpes or vaccinia viruses, or from various bacterial plasmids, maybe used for delivery of nucleotide sequences to the targeted organ,tissue, or cell population. (See, e.g., Di Nicola, M. et al. (1998)Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad.Sci. USA 90(13):6340-6344; Buller, R. M. et al. (1985) Nature317(6040):813-815; McGregor, D. P. et al. (1994) Mol. Immunol.31(3):219-226; and Verma, I. M. and N. Somia (1997) Nature 389:239-242.)The invention is not limited by the host cell employed.

[0171] In bacterial systems, a number of cloning and expression vectorsmay be selected depending upon the use intended for polynucleotidesequences encoding GCREC. For example, routine cloning, subcloning, andpropagation of polynucleotide sequences encoding GCREC can be achievedusing a multifunctional E. coli vector such as PBLUESCRIT (Stratagene,La Jolla Calif.) or PSPORT1 plasmid (Life Technologies). Ligation ofsequences encoding GCREC into the vector's multiple cloning sitedisrupts the lacZ gene, allowing a colorimetric screening procedure foridentification of transformed bacteria containing recombinant molecules.In addition, these vectors may be useful for in vitro transcription,dideoxy sequencing, single strand rescue with helper phage, and creationof nested deletions in the cloned sequence. (See, e.g., Van Heeke, G.and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509.) When largequantities of GCREC are needed, e.g. for the production of antibodies,vectors which direct high level expression of GCREC may be used. Forexample, vectors containing the strong, inducible SP6 or T7bacteriophage promoter may be used.

[0172] Yeast expression systems may be used for production of GCREC. Anumber of vectors containing constitutive or inducible promoters, suchas alpha factor, alcohol oxidase, and PGH promoters, may be used in theyeast Saccharomyces cerevisiae or Pichia pastoris. In addition, suchvectors direct either the secretion or intracellular retention ofexpressed proteins and enable integration of foreign sequences into thehost genome for stable propagation. (See, e.g., Ausubel, 1995, supra;Bitter, G. A. et al. (1987) Methods Enzymol. 153:516-544; and Scorer, C.A. et al. (1994) Bio/Technology 12:181-184.)

[0173] Plant systems may also be used for expression of GCREC.Transcription of sequences encoding GCREC may be driven by viralpromoters, e.g., the 35S and 19S promoters of CaMV used alone or incombination with the omega leader sequence from TMV (Takamatsu, N.(1987) EMBO J. 6:307-311). Alternatively, plant promoters such as thesmall subunit of RUBISCO or heat shock promoters may be used. (See,e.g., Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al.(1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl.Cell Differ. 17:85-105.) These constructs can be introduced into plantcells by direct DNA transformation or pathogen-mediated transfection.(See, e.g., The McGraw Hill Yearbook of Science and Technology (1992)McGraw Hill, New York N.Y., pp. 191-196.)

[0174] In mammalian cells, a number of viral-based expression systemsmay be utilized. In cases where an adenovirus is used as an expressionvector, sequences encoding GCREC may be ligated into an adenovirustranscription/translation complex consisting of the late promoter andtripartite leader sequence. Insertion in a non-essential E1 or E3 regionof the viral genome may be used to obtain infective virus whichexpresses GCREC in host cells. (See, e.g., Logan, J. and T. Shenk (1984)Proc. Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcriptionenhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used toincrease expression in mammalian host cells. SV40 or EBV-based vectorsmay also be used for high-level protein expression.

[0175] Human artificial chromosomes (HACs) may also be employed todeliver larger fragments of DNA than can be contained in and expressedfrom a plasmid. HACs of about 6 kb to 10 Mb are constructed anddelivered via conventional delivery methods (liposomes, polycationicamino polymers, or vesicles) for therapeutic purposes. (See, e.g.,Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355.)

[0176] For long term production of recombinant proteins in mammaliansystems, stable expression of GCREC in cell lines is preferred. Forexample, sequences encoding GCREC can be transformed into cell linesusing expression vectors which may contain viral origins of replicationand/or endogenous expression elements and a selectable marker gene onthe same or on a separate vector. Following the introduction of thevector, cells may be allowed to grow for about 1 to 2 days in enrichedmedia before being switched to selective media. The purpose of theselectable marker is to confer resistance to a selective agent, and itspresence allows growth and recovery of cells which successfully expressthe introduced sequences. Resistant clones of stably transformed cellsmay be propagated using tissue culture techniques appropriate to thecell type.

[0177] Any number of selection systems may be used to recovertransformed cell lines. These include, but are not limited to, theherpes simplex virus thymidine kinase and adeninephosphonbosyltransferase genes, for use in tk and apr cells,respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232;Lowy, I. et al. (1980) Cell 22:817-823.) Also, antimetabolite,antibiotic, or herbicide resistance can be used as the basis forselection. For example, dhfr confers resistance to methotrexate; neoconfers resistance to the aminoglycosides neomycin and G-418; and alsand pat confer resistance to chlorsulfuron and phosphinotricinacetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980)Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al.(1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have beendescribed, e.g., typB and hisD, which alter cellular requirements formetabolites. (See, e.g., Hartman, S. C. and R. C. Mulligan (1988) Proc.Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins,green fluorescent proteins (GFP; Clontech), β glucuronidase and itssubstrate β-glucuronide, or luciferase and its substrate luciferin maybe used. These markers can be used not only to identify transformants,but also to quantify the amount of transient or stable proteinexpression attributable to a specific vector system. (See, e.g., Rhodes,C. A. (1995) Methods Mol. Biol. 55:121-131.)

[0178] Although the presence/absence of marker gene expression suggeststhat the gene of interest is also present, the presence and expressionof the gene may need to be confirmed. For example, if the sequenceencoding GCREC is inserted within a marker gene sequence, transformedcells containing sequences encoding GCREC can be identified by theabsence of marker gene function. Alternatively, a marker gene can beplaced in tandem with a sequence encoding GCREC under the control of asingle promoter. Expression of the marker gene in response to inductionor selection usually indicates expression of the tandem gene as well.

[0179] In general, host cells that contain the nucleic acid sequenceencoding GCREC and that express GCREC may be identified by a variety ofprocedures known to those of skill in the art. These procedures include,but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCRamplification, and protein bioassay or immunoassay techniques whichinclude membrane, solution, or chip based technologies for the detectionand/or quantification of nucleic acid or protein sequences.

[0180] Immunological methods for detecting and measuring the expressionof GCREC using either specific polyclonal or monoclonal antibodies areknown in the art. Examples of such techniques include enzyme-linkedimmunosorbent assays (ELISAs), radioimmunoassays (RIAs), andfluorescence activated cell sorting (FACS). A two-site, monoclonal-basedimmunoassay utilizing monoclonal antibodies reactive to twonon-interfering epitopes on GCREC is preferred, but a competitivebinding assay may be employed. These and other assays are well known inthe art. (See, e.g., Hampton, R. et al. (1990) Serological Methods, aLaboratory Manual, APS Press, St. Paul Minn., Sect IV; Coligan, J. E. etal. (1997) Current Protocols in Immunology, Greene Pub. Associates andWiley-Interscience, New York N.Y.; and Pound, J. D. (1998)Immunochemical Protocols, Humana Press, Totowa N.J.)

[0181] A wide variety of labels and conjugation techniques are known bythose skilled in the art and may be used in various nucleic acid andamino acid assays. Means for producing labeled hybridization or PCRprobes for detecting sequences related to polynucleotides encoding GCRECinclude oligolabeling, nick translation, end-labeling, or PCRamplification using a labeled nucleotide. Alternatively, the sequencesencoding GCREC, or any fragments thereof, may be cloned into a vectorfor the production of an mRNA probe. Such vectors are known in the art,are commercially available, and may be used to synthesize RNA probes invitro by addition of an appropriate RNA polymerase such as T7, T3, orSP6 and labeled nucleotides. These procedures may be conducted using avariety of commercially available kits, such as those provided byAmersham Pharmacia Biotech, Promega (Madison Wis.), and US Biochemical.Suitable reporter molecules or labels which may be used for ease ofdetection include radionuclides, enzymes, fluorescent, chemiluminescent,or chromogenic agents, as well as substrates, cofactors, inhibitors,magnetic particles, and the like.

[0182] Host cells transformed with nucleotide sequences encoding GCRECmaybe cultured under conditions suitable for the expression and recoveryof the protein from cell culture. The protein produced by a transformedcell may be secreted or retained intracellularly depending on thesequence and/or the vector used. As will be understood by those of skillin the art, expression vectors containing polynucleotides which encodeGCREC may be designed to contain signal sequences which direct secretionof GCREC through a prokaryotic or eukaryotic cell membrane.

[0183] In addition, a host cell strain may be chosen for its ability tomodulate expression of the inserted sequences or to process theexpressed protein in the desired fashion. Such modifications of thepolypeptide include, but are not limited to, acetylation, carboxylation,glycosylation, phosphorylation, lipidation, and acylation.Post-translational processing which cleaves a “prepro” or “pro” form ofthe protein may also be used to specify protein targeting, folding,and/or activity. Different host cells which have specific cellularmachinery and characteristic mechanisms for post-translationalactivities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available fromthe American Type Culture Collection (ATCC, Manassas Va.) and may bechosen to ensure the correct modification and processing of the foreignprotein.

[0184] In another embodiment of the invention, natural, modified, orrecombinant nucleic acid sequences encoding GCREC may be ligated to aheterologous sequence resulting in translation of a fusion protein inany of the aforementioned host systems. For example, a chimeric GCRECprotein containing a heterologous moiety that can be recognized by acommercially available antibody may facilitate the screening of peptidelibraries for inhibitors of GCREC activity. Heterologous protein andpeptide moieties may also facilitate purification of fusion proteinsusing commercially available affinity matrices. Such moieties include,but are not limited to, glutathione S-transferase (GST), maltose bindingprotein (MBP), thioredoxin (Trx), calmodulin binding peptide (CBP),6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and6-His enable purification of their cognate fusion proteins onimmobilized glutathione, maltose, phenylarsine oxide, calmodulin, andmetal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA)enable immunoaffinity purification of fusion proteins using commerciallyavailable monoclonal and polyclonal antibodies that specificallyrecognize these epitope tags. A fusion protein may also be engineered tocontain a proteolytic cleavage site located between the GCREC encodingsequence and the heterologous protein sequence, so that GCREC may becleaved away from the heterologous moiety following purification.Methods for fusion protein expression and purification are discussed inAusubel (1995, supra, ch. 10). A variety of commercially available kitsmay also be used to facilitate expression and purification of fusionproteins.

[0185] In a further embodiment of the invention, synthesis ofradiolabeled GCREC may be achieved in vitro using the TNT rabbitreticulocyte lysate or wheat germ extract system (Promega). Thesesystems couple transcription and translation of protein-coding sequencesoperably associated with the T7, T3, or SP6 promoters. Translation takesplace in the presence of a radiolabeled amino acid precursor, forexample, ³⁵S-methionine.

[0186] GCREC of the present invention or fragments thereof may be usedto screen for compounds that specifically bind to GCREC. At least oneand up to a plurality of test compounds may be screened for specificbinding to GCREC. Examples of test compounds include antibodies,oligonucleotides, proteins (e.g., receptors), or small molecules.

[0187] In one embodiment, the compound thus identified is closelyrelated to the natural ligand of GCREC, e.g., a ligand or fragmentthereof, a natural substrate, a structural or functional mimetic, or anatural binding partner. (See, e.g., Coligan, J. E. et al. (1991)Current Protocols in Immunology 1(2): Chapter 5.) Similarly, thecompound can be closely related to the natural receptor to which GCRECbinds, or to at least a fragment of the receptor, e.g., the ligandbinding site. In either case, the compound can be rationally designedusing known techniques. In one embodiment, screening for these compoundsinvolves producing appropriate cells which express GCREC, either as asecreted protein or on the cell membrane. Preferred cells include cellsfrom mammals, yeast, Drosophila, or E. coli. Cells expressing GCREC orcell membrane fractions which contain GCREC are then contacted with atest compound and binding, stimulation, or inhibition of activity ofeither GCREC or the compound is analyzed.

[0188] An assay may simply test binding of a test compound to thepolypeptide, wherein binding is detected by a fluorophore, radioisotope,enzyme conjugate, or other detectable label. For example, the assay maycomprise the steps of combining at least one test compound with GCREC,either in solution or affixed to a solid support, and detecting thebinding of GCREC to the compound. Alternatively, the assay may detect ormeasure binding of a test compound in the presence of a labeledcompetitor. Additionally, the assay may be carried out using cell-freepreparations, chemical libraries, or natural product mixtures, and thetest compound(s) may be free in solution or affixed to a solid support.

[0189] GCREC of the present invention or fragments thereof may be usedto screen for compounds that modulate the activity of GCREC. Suchcompounds may include agonists, antagonists, or partial or inverseagonists. In one embodiment, an assay is performed under conditionspermissive for GCREC activity, wherein GCREC is combined with at leastone test compound, and the activity of GCREC in the presence of a testcompound is compared with the activity of GCREC in the absence of thetest compound. A change in the activity of GCREC in the presence of thetest compound is indicative of a compound that modulates the activity ofGCREC. Alternatively, a test compound is combined with an in vitro orcell-free system comprising GCREC under conditions suitable for GCRECactivity, and the assay is performed. In either of these assays, a testcompound which modulates the activity of GCREC may do so indirectly andneed not come in direct contact with the test compound. At least one andup to a plurality of test compounds may be screened.

[0190] In another embodiment, polynucleotides encoding GCREC or theirmammalian homologs may be “knocked out” in an animal model system usinghomologous recombination in embryonic stem (ES) cells. Such techniquesare well known in the art and are useful for the generation of animalmodels of human disease. (See, e.g., U.S. Pat. No. 5,175,383 and U.S.Pat. No. 5,767,337.) For example, mouse ES cells, such as the mouse129/SvJ cell line, are derived from the early mouse embryo and grown inculture. The ES cells are transformed with a vector containing the geneof interest disrupted by a marker gene, e.g., the neomycinphosphotransferase gene (neo; Capecchi, M. R. (1989) Science244:1288-1292). The vector integrates into the corresponding region ofthe host genome by homologous recombination. Alternatively, homologousrecombination takes place using the Cre-loxP system to knockout a geneof interest in a tissue- or developmental stage-specific manner (Marth,J. D. (1996) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997)Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identifiedand microinjected into mouse cell blastocysts such as those from theC57BL/6 mouse strain. The blastocysts are surgically transferred topseudopregnant dams, and the resulting chimeric progeny are genotypedand bred to produce heterozygous or homozygous strains. Transgenicanimals thus generated may be tested with potential therapeutic or toxicagents.

[0191] Polynucleotides encoding GCREC may also be manipulated in vitroin ES cells derived from human blastocysts. Human ES cells have thepotential to differentiate into at least eight separate cell lineagesincluding endoderm, mesoderm, and ectodermal cell types. These celllineages differentiate into, for example, neural cells, hematopoieticlineages, and cardiomyocytes (Thomson, J. A. et al. (1998) Science282:1145-1147).

[0192] Polynucleotides encoding GCREC can also be used to create“knockin” humanized animals (pigs) or transgenic animals (mice or rats)to model human disease. With knockin technology, a region of apolynucleotide encoding GCREC is injected into animal ES cells, and theinjected sequence integrates into the animal cell genome. Transformedcells are injected into blastulae, and the blastulae are implanted asdescribed above. Transgenic progeny or inbred lines are studied andtreated with potential pharmaceutical agents to obtain information ontreatment of a human disease. Alternatively, a mammal inbred tooverexpress GCREC, e.g., by secreting GCREC in its milk, may also serveas a convenient source of that protein (Janne, J. et al. (1998)Biotechnol. Annu. Rev. 4:55-74).

[0193] Therapeutics

[0194] Chemical and structural similarity, e.g., in the context ofsequences and motifs, exists between regions of GCREC and G-proteincoupled receptors. In addition, the expression of GCREC is closelyassociated with tissues such as aorta, coronary artery plaque,cerebellum, lymph nodes, muscle, neurological, tonsil, bladder tumor,diseased breast, testicle tumor, spleen, ovary, parathyroid, ileum,breast skin, and sigmoid colon. Therefore, GCREC appears to play a rolein cell proliferative, neurological, cardiovascular, gastrointestinal,autoimmuneimflammatory, and metabolic disorders, and viral infections.In the treatment of disorders associated with increased GCREC expressionor activity, it is desirable to decrease the expression or activity ofGCREC. In the treatment of disorders associated with decreased GCRECexpression or activity, it is desirable to increase the expression oractivity of GCREC.

[0195] Therefore, in one embodiment, GCREC or a fragment or derivativethereof may be administered to a subject to treat or prevent a disorderassociated with decreased expression or activity of GCREC. Examples ofsuch disorders include, but are not limited to, a cell proliferativedisorder such as actinic keratosis, arteriosclerosis, atherosclerosis,bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTID),myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera,psoriasis, primary thrombocythemia, and cancers includingadenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma,teratocarcinoma, and, in particular, cancers of the adrenal gland,bladder, bone, bone marrow, brain, breast, cervix, gall bladder,ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle,ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin,spleen, testis, thymus, thyroid, and uterus; a neurological disordersuch as epilepsy, ischemic cerebrovascular disease, stroke, cerebralneoplasms, Alzheimer's disease, Pick's disease, Huntington's disease,dementia, Parkinson's disease and other extrapyramidal disorders,amyotrophic lateral sclerosis and other motor neuron disorders,progressive neural muscular atrophy, retinitis pigmentosa, hereditaryataxias, multiple sclerosis and other demyelinating diseases, bacterialand viral meningitis, brain abscess, subdural empyema, epidural abscess,suppurative intracranial thrombophliebitis, myelitis and radiculitis,viral central nervous system disease, prion diseases including kuru,Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, nutritional and metabolic diseases of thenervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinalhemangioblastomatosis, encephalotrigeminal syndrome, mental retardationand other developmental disorders of the central nervous system,cerebral palsy, neuroskeletal disorders, autonomic nervous systemdisorders, cranial nerve disorders, spinal cord diseases, musculardystrophy and other neuromuscular disorders, peripheral nervous systemdisorders, dermatomyositis and polymyositis, inherited, metabolic,endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis,mental disorders including mood, anxiety, and schizophrenic disorders,seasonal affective disorder (SAD), akathesia, amnesia, catatonia,diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses,postherpetic neuralgia, Tourette's disorder, progressive supranuclearpalsy, corticobasal degeneration, and familial frontotemporal dementia;a cardiovascular disorder such as arteriovenous fistula,atherosclerosis, hypertension, vasculitis, Raynaud's disease, aneurysms,arterial dissections, varicose veins, thrombophlebitis andphlebothrombosis, vascular tumors, complications of thrombolysis,balloon angioplasty, vascular replacement, and coronary artery bypassgraft surgery, congestive heart failure, ischemic heart disease, anginapectoris, myocardial infarction, hypertensive heart disease,degenerative valvular heart disease, calcific aortic valve stenosis,congenitally bicuspid aortic valve, mitral annular calcification, mitralvalve prolapse, rheumatic fever and rheumatic heart disease, infectiveendocarditis, nonbacterial thrombotic endocarditis, endocarditis ofsystemic lupus erythematosus, carcinoid heart disease, cardiomyopathy,myocarditis, pericarditis, neoplastic heart disease, congenital heartdisease, and complications of cardiac transplantation; agastrointestinal disorder such as dysphagia, peptic esophagitis,esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia,indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis,gastroparesis, antral or pyloric edema, abdominal angina, pyrosis,gastroenteritis, intestinal obstruction, infections of the intestinaltract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis,pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis,hyperbilirubinemia, cirrhosis, passive congestion of the liver,hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis,Crohn's disease, Whipple's disease, Mallory-Weiss syndrome, coloniccarcinoma, colonic obstruction, irritable bowel syndrome, short bowelsyndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquiredimmunodeficiency syndrome (AIDS) enteropathy, jaundice, hepaticencephalopathy, hepatorenal syndrome, hepatic steatosis,hemochromatosis, Wilson's disease, alpha₁-antitrypsin deficiency, Reye'ssyndrome, primary sclerosing cholangitis, liver infarction, portal veinobstruction and thrombosis, centrilobular necrosis, peliosis hepatis,hepatic vein thrombosis, veno-occlusive disease, preeclampsia,eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis ofpregnancy, and hepatic tumors including nodular hyperplasias, adenomas,and carcinomas; an autoimmuneimflammatory disorder such as acquiredimmunodeficiency syndrome (AIDS), Addison's disease, adult respiratorydistress syndrome, allergies, ankylosing spondylitis, amyloidosis,anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmunethyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy (APECED), bronchitis, cholecystitis, contact dermatitis,Crohn's disease, atopic dermatitis, dermatomyositis, diabetes mellitus,emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosisfetalis, erythema nodosum, atrophic gastritis, glomerulonephritis,Goodpasture's syndrome, gout, Graves′ disease, Hashimoto's thyroiditis,hypereosinophilia, irritable bowel syndrome, multiple sclerosis,myasthenia gravis, myocardial or pericardial inflammation,osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis,Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjögren'ssyndrome, systemic anaphylaxis, systemic lupus erythematosus, systemicsclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Wernersyndrome, complications of cancer, hemodialysis, and extracorporealcirculation, viral, bacterial, fungal, parasitic, protozoal, andhelminthic infections, and trauma; a metabolic disorder such asdiabetes, obesity, and osteoporosis; and an infection by a viral agentclassified as adenovirus, arenavirus, bunyavirus, calicivirus,coronavirus, filovirus, hepadnavirus, herpesvirus, flavivirus,orthomyxovirus, parvovirus, papovavirus, paramyxovirus, picornavirus,poxvirus, reovirus, retrovirus, rhabdovirus, and tongavirus.

[0196] In another embodiment, a vector capable of expressing GCREC or afragment or derivative thereof may be administered to a subject to treator prevent a disorder associated with decreased expression or activityof GCREC including, but not limited to, those described above.

[0197] In a further embodiment, a composition comprising a substantiallypurified GCREC in conjunction with a suitable pharmaceutical carrier maybe administered to a subject to treat or prevent a disorder associatedwith decreased expression or activity of GCREC including, but notlimited to, those provided above.

[0198] In still another embodiment, an agonist which modulates theactivity of GCREC may be administered to a subject to treat or prevent adisorder associated with decreased expression or activity of GCRECincluding, but not limited to, those listed above.

[0199] In a further embodiment, an antagonist of GCREC may beadministered to a subject to treat or prevent a disorder associated withincreased expression or activity of GCREC. Examples of such disordersinclude, but are not limited to, those cell proliferative, neurological,cardiovascular, gastrointestinal, autoimmuneimflammatory, and metabolicdisorders, and viral infections described above. In one aspect, anantibody which specifically binds GCREC may be used directly as anantagonist or indirectly as a targeting or delivery mechanism forbringing a pharmaceutical agent to cells or tissues which express GCREC.

[0200] In an additional embodiment, a vector expressing the complementof the polynucleotide encoding GCREC may be administered to a subject totreat or prevent a disorder associated with increased expression oractivity of GCREC including, but not limited to, those described above.

[0201] In other embodiments, any of the proteins, antagonists,antibodies, agonists, complementary sequences, or vectors of theinvention may be administered in combination with other appropriatetherapeutic agents. Selection of the appropriate agents for use incombination therapy may be made by one of ordinary skill in the art,according to conventional pharmaceutical principles. The combination oftherapeutic agents may act synergistically to effect the treatment orprevention of the various disorders described above. Using thisapproach, one may be able to achieve therapeutic efficacy with lowerdosages of each agent, thus reducing the potential for adverse sideeffects.

[0202] An antagonist of GCREC may be produced using methods which aregenerally known in the art. In particular, purified GCREC may be used toproduce antibodies or to screen libraries of pharmaceutical agents toidentify those which specifically bind GCREC. Antibodies to GCREC mayalso be generated using methods that are well known in the art. Suchantibodies may include, but are not limited to, polyclonal, monoclonal,chimeric, and single chain antibodies, Fab fragments, and fragmentsproduced by a Fab expression library. Neutralizing antibodies (i.e.,those which inhibit dimer formation) are generally preferred fortherapeutic use. Single chain antibodies (e.g., from camels or llamas)may be potent enzyme inhibitors and may have advantages in the design ofpeptide mimetics, and in the development of immmuno-adsorbents andbiosensors (Muyldermans, S. (2001) J. Biotechnol. 74:277-302).

[0203] For the production of antibodies, various hosts including goats,rabbits, rats, rice, camels, dromedaries, llamas, humans, and others maybe immunized by injection with GCREC or with any fragment oroligopeptide thereof which has immunogenic properties. Depending on thehost species, various adjuvants may be used to increase immunologicalresponse. Such adjuvants include, but are not limited to, Freund's,mineral gels such as aluminum hydroxide, and surface active substancessuch as lysolecithin, pluronic polyols, polyanions, peptides, oilemulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG(bacilli Calmette-Guerin) and Corvnebacterium parvum are especiallypreferable.

[0204] It is preferred that the oligopeptides, peptides, or fragmentsused to induce antibodies to GCREC have an amino acid sequenceconsisting of at least about 5 amino acids, and generally will consistof at least about 10 amino acids. It is also preferable that theseoligopeptides, peptides, or fragments are identical to a portion of theamino acid sequence of the natural protein. Short stretches of GCRECamino acids may be fused with those of another protein, such as KLH, andantibodies to the chimeric molecule may be produced.

[0205] Monoclonal antibodies to GCREC may be prepared using anytechnique which provides for the production of antibody molecules bycontinuous cell lines in culture. These include, but are not limited to,the hybridoma technique, the human B-cell hybridoma technique, and theEBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature256:495-497; Kozbor, D. et al. (1985) J. Immunol. Methods 81:31-42;Cote, R. J. et al. (1983) Proc. Natl. Acad. Sci. USA 80:2026-2030; andCole, S. P. et al. (1984) Mol. Cell Biol. 62:109-120.)

[0206] In addition, techniques developed for the production of “chimericantibodies,” such as the splicing of mouse antibody genes to humanantibody genes to obtain a molecule with appropriate antigen specificityand biological activity, can be used. (See, e.g., Morrison, S. L. et al.(1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al.(1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature314:452-454.) Alternatively, techniques described for the production ofsingle chain antibodies may be adapted, using methods known in the art,to produce GCREC-specific single chain antibodies. Antibodies withrelated specificity, but of distinct idiotypic composition, may begenerated by chain shuffling from random combinatorial immunoglobulinlibraries. (See, e.g., Burton, D. R. (1991) Proc. Natl. Acad. Sci. USA88:10134-10137.)

[0207] Antibodies may also be produced by inducing in vivo production inthe lymphocyte population or by screening immunoglobulin libraries orpanels of highly specific binding reagents as disclosed in theliterature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci.USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.)

[0208] Antibody fragments which contain specific binding sites for GCRECmay also be generated. For example, such fragments include, but are notlimited to, F(ab′)₂ fragments produced by pepsin digestion of theantibody molecule and Fab fragments generated by reducing the disulfidebridges of the F(ab′)2 fragments. Alternatively, Fab expressionlibraries may be constructed to allow rapid and easy identification ofmonoclonal Fab fragments with the desired specificity. (See, e.g., Huse,W. D. et al. (1989) Science 246:1275-1281.)

[0209] Various immunoassays may be used for screening to identifyantibodies having the desired specificity. Numerous protocols forcompetitive binding or immunoradiometric assays using either polyclonalor monoclonal antibodies with established specificities are well knownin the art. Such immunoassays typically involve the measurement ofcomplex formation between GCREC and its specific antibody. A two-site,monoclonal-based immunoassay utilizing monoclonal antibodies reactive totwo non-interfering GCREC epitopes is generally used, but a competitivebinding assay may also be employed (Pound, supra).

[0210] Various methods such as Scatchard analysis in conjunction withradioimmunoassay techniques may be used to assess the affinity ofantibodies for GCREC. Affinity is expressed as an association constant,K_(a), which is defined as the molar concentration of GCREC-antibodycomplex divided by the molar concentrations of free antigen and freeantibody under equilibrium conditions. The K_(a) determined for apreparation of polyclonal antibodies, which are heterogeneous in theiraffinities for multiple GCREC epitopes, represents the average affinity,or avidity, of the antibodies for GCREC. The K_(a) determined for apreparation of monoclonal antibodies, which are monospecific for aparticular GCREC epitope, represents a true measure of affinity.High-affinity antibody preparations with K_(a) ranging from about 10⁹ to10¹² L/mole are preferred for use in immunoassays in which theGCREC-antibody complex must withstand rigorous manipulations.Low-affinity antibody preparations with K_(a) ranging from about 10⁶ to10⁷ L/mole are preferred for use in immunopurification and similarprocedures which ultimately require dissociation of GCREC, preferably inactive form, from the antibody (Catty, D. (1988) Antibodies, Volume I: APractical Approach, IRL Press, Washington D.C.; Liddell, J. E. and A.Cryer (1991) A Practical Guide to Monoclonal Antibodies, John Wiley &Sons, New York N.Y.).

[0211] The titer and avidity of polyclonal antibody preparations may befurther evaluated to determine the quality and suitability of suchpreparations for certain downstream applications. For example, apolyclonal antibody preparation containing at least 1-2 mg specificantibody/ml, preferably 5-10 mg specific antibody/ml, is generallyemployed in procedures requiring precipitation of GCREC-antibodycomplexes. Procedures for evaluating antibody specificity, titer, andavidity, and guidelines for an body quality and usage in variousapplications, are generally available. (See, e.g., Catty, supra, andColigan et al. supra.)

[0212] In another embodiment of the invention, the polynucleotidesencoding GCREC, or any fragment or complement thereof, may be used fortherapeutic purposes. In one aspect, modifications of gene expressioncan be achieved by designing complementary sequences or antisensemolecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding orregulatory regions of the gene encoding GCREC. Such technology is wellknown in the art, and antisense oligonucleotides or larger fragments canbe designed from various locations along the coding or control regionsof sequences encoding GCREC. (See, e.g., Agrawal, S., ed. (1996)Antisense Therapeutics, Humana Press Inc., Totawa N.J.)

[0213] In therapeutic use, any gene delivery system suitable forintroduction of the antisense sequences into appropriate target cellscan be used. Antisense sequences can be delivered intracellularly in theform of an expression plasmid which, upon transcription, produces asequence complementary to at least a portion of the cellular sequenceencoding the target protein. (See, e.g., Slater, J. E. et al. (1998) J.Allergy Clin. Immunol. 102(3):469-475; and Scanlon, K. J. et al. (1995)9(13):1288-1296.) Antisense sequences can also be introducedintracellularly through the use of viral vectors, such as retrovirus andadeno-associated virus vectors. (See, e.g., Miller, A. D. (1990) Blood76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol.Ther. 63(3):323-347.) Other gene delivery mechanisms includeliposome-derived systems, artificial viral envelopes, and other systemsknown in the art. (See, e.g., Rossi, J. J. (1995) Br. Med. Bull.51(1):217-225; Boado, R. J. et al. (1998) J. Pharm. Sci.87(11):1308-1315; and Morris, M. C. et al. (1997) Nucleic Acids Res.25(14):2730-2736.)

[0214] In another embodiment of the invention, polynucleotides encodingGCREC may be used for somatic or geriline gene therapy. Gene therapy maybe performed to (i) correct a genetic deficiency (e.g., in the cases ofsevere combined inmnunodeficiency (SCHD)-X1 disease characterized byX-linked inheritance (Cavazzana-Calvo, M. et al. (2000) Science288:669-672), severe combined immunodeficiency syndrome associated withan inherited adenosine deaminase (ADA) deficiency (Blaese, R. M. et al.(1995) Science 270:475-480; Bordignon, C. et al. (1995) Science270:470-475), cystic fibrosis (Zabner, J. et al. (1993) Cell 75:207-216;Crystal, R. G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R. G.et al. (1995) Hum. Gene Therapy 6:667-703), thalassamias, familialhypercholesterolemia, and hemophilia resulting from Factor Vm or FactorIX deficiencies (Crystal, R. G. (1995) Science 270:404-410; Verma, I. M.and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionallylethal gene product (e.g., in the case of cancers which result fromunregulated cell proliferation), or (iii) express a protein whichaffords protection against intracellular parasites (e.g., against humanretroviruses, such as human immunodeficiency virus (HIV) (Baltimore, D.(1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad.Sci. USA 93:11395-11399), hepatitis B or C virus (HBV, HCV); fungalparasites, such as Candida albicans and Paracoccidioides brasiliensis;and protozoan parasites such as Plasmodium falcinarum and Trypanosomacruzi). In the case where a genetic deficiency in GCREC expression orregulation causes disease, the expression of GCREC from an appropriatepopulation of transduced cells may alleviate the clinical manifestationscaused by the genetic deficiency.

[0215] In a further embodiment of the invention, diseases or disorderscaused by deficiencies in GCREC are treated by constructing mammalianexpression vectors encoding GCREC and introducing these vectors bymechanical means into GCREC-deficient cells. Mechanical transfertechnologies for use with cells in vivo or ex vitro include (i) directDNA microinjection into individual cells, (ii) ballistic gold particledelivery, (iii) liposome-mediated transfection, (iv) receptor-mediatedgene transfer, and (v) the use of DNA transposons (Morgan, R. A. and W.F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivics, Z. (1997) Cell91:501-510; Boulay, J-L. and H. Récipon (1998) Curr. Opin. Biotechnol.9:445-450).

[0216] Expression vectors that may be effective for the expression ofGCREC include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2,PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif.),PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), andPTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo AltoCalif.). GCREC maybe expressed using (i) a constitutively activepromoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV),SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an induciblepromoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H.Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al.(1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998)Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REXplasmid (Invitrogen)); the ecdysone-inducible promoter (available in theplasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin induciblepromoter; or the RU486/lifepristone inducible promoter (Rossi, F. M. V.and H. M. Blau, supra)), or (iii) a tissue-specific promoter or thenative promoter of the endogenous gene encoding GCREC from a normalindividual.

[0217] Commercially available liposome transformation kits (e.g., thePERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow onewith ordinary skill in the art to deliver polynucleotides to targetcells in culture and require minimal effort to optimize experimentalparameters. In the alternative, transformation is performed using thecalcium phosphate method (Graham, F. L. and A. J. Eb (1973) Virology52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J.1:841-845). The introduction of DNA to primary cells requiresmodification of these standardized mammalian transfection protocols.

[0218] In another embodiment of the invention, diseases or disorderscaused by genetic defects with respect to GCREC expression are treatedby constructing a retrovirus vector consisting of (i) the polynucleotideencoding GCREC under the control of an independent promoter or theretrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNApackaging signals, and (iii) a Rev-responsive element (RRE) along withadditional retrovirus cis-acting RNA sequences and coding sequencesrequired for efficient vector propagation. Retrovirus vectors (e.g., PFBand PFBNEO) are commercially available (Stratagene) and are based onpublished data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA92:6733-6737), incorporated by reference herein. The vector ispropagated in an appropriate vector producing cell line (VPCL) thatexpresses an envelope gene with a tropism for receptors on the targetcells or a promiscuous envelope protein such as VSVg (Armentano, D. etal. (1987) J. Virol. 61:1647-1650; Bender, M. A. et al. (1987) J. Virol.61:1639-1646; Adam, M. A. and A. D. Miller (1988) J. Virol.62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey,R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 toRigg (“Method for obtaining retrovirus packaging cell lines producinghigh transducing efficiency retroviral supernatant”) discloses a methodfor obtaining retrovirus packaging cell lines and is hereby incorporatedby reference. Propagation of retrovirus vectors, transduction of apopulation of cells (e.g., CD4⁺ T-cells), and the return of transducedcells to a patient are procedures well known to persons skilled in theart of gene therapy and have been well documented (Ranga, U. et al.(1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood89:2259-2267; Bonyhadi, M. L. (1997) J. Virol. 71:4707-4716; Ranga, U.et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997)Blood 89:2283-2290).

[0219] In the alternative, an adenovirus-based gene therapy deliverysystem is used to deliver polynucleotides encoding GCREC to cells whichhave one or more genetic abnormalities with respect to the expression ofGCREC. The construction and packaging of adenovirus-based vectors arewell known to those with ordinary skill in the art. Replicationdefective adenovirus vectors have proven to be versatile for importinggenes encoding immunoregulatory proteins into intact islets in thepancreas (Csete, M. E. et al. (1995) Transplantation 27:263-268).Potentially useful adenoviral vectors are described in U.S. Pat. No.5,707,618 to Arinentano (“Adenovirus vectors for gene therapy”), herebyincorporated by reference. For adenoviral vectors, see also Antinozzi,P. A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I. M. and N.Somia (1997) Nature 18:389:239-242, both incorporated by referenceherein.

[0220] In another alternative, a herpes-based, gene therapy deliverysystem is used to deliver polynucleotides encoding GCREC to target cellswhich have one or more genetic abnormalities with respect to theexpression of GCREC. The use of herpes simplex virus (HSV)-based vectorsmay be especially valuable for introducing GCREC to cells of the centralnervous system, for which HSV has a tropism. The construction andpackaging of herpes-based vectors are well known to those with ordinaryskill in the art. A replication-competent herpes simplex virus (HSV)type 1-based vector has been used to deliver a reporter gene to the eyesof primates (Liu, X. et al. (1999) Exp. Eye Res. 169:385-395). Theconstruction of a HSV-1 virus vector has also been disclosed in detailin U.S. Pat. No. 5,804,413 to DeLuca (“Herpes simplex virus strains forgene transfer”), which is hereby incorporated by reference. U.S. Pat.No. 5,804,413 teaches the use of recombinant HSV d92 which consists of agenome containing at least one exogenous gene to be transferred to acell under the control of the appropriate promoter for purposesincluding human gene therapy. Also taught by this patent are theconstruction and use of recombinant HSV strains deleted for ICP4, ICP27and ICP22. For HSV vectors, see also Goins, W. F. et al. (1999) J.Virol. 73:519-532 and Xu, H. et al. (1994) Dev. Biol. 163:152-161,hereby incorporated by reference. The manipulation of cloned herpesvirussequences, the generation of recombinant virus following thetransfection of multiple plasmids containing different segments of thelarge herpesvirus genomes, the growth and propagation of herpesvirus,and the infection of cells with herpesvirus are techniques well known tothose of ordinary skill in the art.

[0221] In another alternative, an alphavirus (positive, single-strandedRNA virus) vector is used to deliver polynucleotides encoding GCREC totarget cells. The biology of the prototypic alphavirus, Semliki ForestVirus (SFV), has been studied extensively and gene transfer vectors havebeen based on the SFV genome (Garoff, H. and K.-J. Li (1998) Curr. Opin.Biotechnol. 9:464-469). During alphavirus RNA replication, a subgenomicRNA is generated that normally encodes the viral capsid proteins. Thissubgenomic RNA replicates to higher levels than the full length genomicRNA, resulting in the overproduction of capsid proteins relative to theviral proteins with enzymatic activity (e.g., protease and polymerase).Similarly, inserting the coding sequence for GCREC into the alphavirusgenome in place of the capsid-coding region results in the production ofa large number of GCREC-coding RNAs and the synthesis of high levels ofGCREC in vector transduced cells. While alphavirus infection istypically associated with cell lysis within a few days, the ability toestablish a persistent infection in hamster normal kidney cells (BHK-21)with a variant of Sindbis virus (SIN) indicates that the lyticreplication of alphaviruses can be altered to suit the needs of the genetherapy application (Dryga, S. A. et al. (1997) Virology 228:74-83). Thewide host range of alphaviruses will allow the introduction of GCRECinto a variety of cell types. The specific transduction of a subset ofcells in a population may require the sorting of cells prior totransduction. The methods of manipulating infectious cDNA clones ofalphaviruses, performing alphavirus cDNA and RNA transfections, andperforming alphavirus infections, are well known to those with ordinaryskill in the art.

[0222] Oligonucleotides derived from the transcription initiation site,e.g., between about positions −10 and +10 from the start site, may alsobe employed to inhibit gene expression. Similarly, inhibition can beachieved using triple helix base-pairing methodology. Triple helixpairing is useful because it causes inhibition of the ability of thedouble helix to open sufficiently for the binding of polymerases,transcription factors, or regulatory molecules. Recent therapeuticadvances using triplex DNA have been described in the literature. (See,e.g., Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr, Molecularand Immunologic Aproaches, Futura Publishing, Mt. Kisco N.Y., pp.163-177.) A complementary sequence or antisense molecule may also bedesigned to block translation of mRNA by preventing the transcript frombinding to ribosomes.

[0223] Ribozymes, enzymatic RNA molecules, may also be used to catalyzethe specific cleavage of RNA. The mechanism of n1bozyme action involvessequence-specific hybridization of the ribozyme molecule tocomplementary target RNA, followed by endonucleolytic cleavage. Forexample, engineered hammerhead motif ribozyme molecules may specificallyand efficiently catalyze endonucleolytic cleavage of sequences encodingGCREC.

[0224] Specific ribozyme cleavage sites within any potential RNA targetare initially identified by scanning the target molecule for ribozymecleavage sites, including the following sequences: GUA, GUU, and GUC.Once identified, short RNA sequences of between 15 and 20ribonucleotides, corresponding to the region of the target genecontaining the cleavage site, may be evaluated for secondary structuralfeatures which may render the oligonucleotide inoperable. Thesuitability of candidate targets may also be evaluated by testingaccessibility to hybridization with complementary oligonucleotides usingribonuclease protection assays.

[0225] Complementary ribonucleic acid molecules and ribozymes of theinvention may be prepared by any method known in the art for thesynthesis of nucleic acid molecules. These include techniques forchemically synthesizing oligonucleotides such as solid phasephosphoramidite chemical synthesis. Alternatively, RNA molecules may begenerated by in vitro and in vivo transcription of DNA sequencesencoding GCREC. Such DNA sequences may be incorporated into a widevariety of vectors with suitable RNA polymerase promoters such as 17 orSP6. Alternatively, these cDNA constructs that synthesize complementaryRNA, constitutively or inducibly, can be introduced into cell lines,cells, or tissues.

[0226] RNA molecules may be modified to increase intracellular stabilityand half-life. Possible modifications include, but are not limited to,the addition of flanking sequences at the 5′ and/or 3′ ends of themolecule, or the use of phosphorothioate or 2′ O-methyl rather thanphosphodiesterase linkages within the backbone of the molecule. Thisconcept is inherent in the production of PNAs and can be extended in allof these molecules by the inclusion of nontraditional bases such asinosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-,and similarly modified forms of adenine, cytidine, guanine, thymine, anduridine which are not as easily recognized by endogenous endonucleases.

[0227] An additional embodiment of the invention encompasses a methodfor screening for a compound which is effective in altering expressionof a polynucleotide encoding GCREC. Compounds which may be effective inaltering expression of a specific polynucleotide may include, but arenot limited to, oligonucleotides, antisense oligonucleotides, triplehelix-forming ohigonucleotides, transcription factors and otherpolypeptide transcriptional regulators, and non-macromolecular chemicalentities which are capable of interacting with specific polynucleotidesequences. Effective compounds may alter polynucleotide expression byacting as either inhibitors or promoters of polynucleotide expression.Thus, in the treatment of disorders associated with increased GCRECexpression or activity, a compound which specifically inhibitsexpression of the polynucleotide encoding GCREC may be therapeuticallyuseful, and in the treatment of disorders associated with decreasedGCREC expression or activity, a compound which specifically promotesexpression of the polynucleotide encoding GCREC may be therapeuticallyuseful.

[0228] At least one, and up to a plurality, of test compounds may bescreened for effectiveness in altering expression of a specificpolynucleotide. A test compound may be obtained by any method commonlyknown in the art, including chemical modification of a compound known tobe effective in altering polynucleotide expression; selection from anexisting, commercially-available or proprietary library ofnaturally-occurring or non-natural chemical compounds; rational designof a compound based on chemical and/or structural properties of thetarget polynucleotide; and selection from a library of chemicalcompounds created combinatorially or randomly. A sample comprising apolynucleotide encoding GCREC is exposed to at least one test compoundthus obtained. The sample may comprise, for example, an intact orpermeabilized cell, or an in vitro cell-free or reconstitutedbiochemical system. Alterations in the expression of a polynucleotideencoding GCREC are assayed by any method commonly known in the art.Typically, the expression of a specific nucleotide is detected byhybridization with a probe having a nucleotide sequence complementary tothe sequence of the polynucleotide encoding GCREC. The amount ofhybridization may be quantified, thus forming the basis for a comparisonof the expression of the polynucleotide both with and without exposureto one or more test compounds. Detection of a change in the expressionof a polynucleotide exposed to a test compound indicates that the testcompound is effective in altering the expression of the polynucleotide.A screen for a compound effective in altering expression of a specificpolynucleotide can be carried out, for example, using aSchizosaccharomyces pombe gene expression system (Atkins, D. et al.(1999) U.S. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic AcidsRes. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. etal. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particularembodiment of the present invention involves screening a combinatoriallibrary of oligonucleotides (such as deoxyribonucleotides,ribonucleotides, peptide nucleic acids, and modified oligonucleotides)for antisense activity against a specific polynucleotide sequence(Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. etal.; (2000) U.S. Pat. No. 6,022,691).

[0229] Many methods for introducing vectors into cells or tissues areavailable and equally suitable for use in vivo, in vitro, and ex vivo.For ex vivo therapy, vectors may be introduced into stem cells takenfrom the patient and clonally propagated for autologous transplant backinto that same patient. Delivery by transfection, by liposomeinjections, or by polycationic amino polymers may be achieved usingmethods which are well known in the art. (See, e.g., Goldman, C. K. etal. (1997) Nat. Biotechnol. 15:462-466.)

[0230] Any of the therapeutic methods described above may be applied toany subject in need of such therapy, including, for example, mammalssuch as humans, dogs, cats, cows, horses, rabbits, and monkeys.

[0231] An additional embodiment of the invention relates to theadministration of a composition which generally comprises an activeingredient formulated with a pharmaceutically acceptable excipient.Excipients may include, for example, sugars, starches, celluloses, gums,and proteins. Various formulations are commonly known and are thoroughlydiscussed in the latest edition of Remington's Pharmaceutical Sciences(Maack Publishing, Easton Pa.). Such compositions may consist of GCREC,antibodies to GCREC, and mimetics, agonists, antagonists, or inhibitorsof GCREC.

[0232] The compositions utilized in this invention may be administeredby any number of routes including, but not limited to, oral,intravenous, intramuscular, intra-arterial, intramedullary, intrathecal,intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal,intranasal, enteral, topical, sublingual, or rectal means.

[0233] Compositions for pulmonary administration may be prepared inliquid or dry powder form. These compositions are generally aerosolizedimmediately prior to inhalation by the patient. In the case of smallmolecules (e.g. traditional low molecular weight organic drugs), aerosoldelivery of fast-acting formulations is well-known in the art. In thecase of macromolecules (e.g. larger peptides and proteins), recentdevelopments in the field of pulmonary delivery via the alveolar regionof the lung have enabled the practical delivery of drugs such as insulinto blood circulation (see, e.g., Patton, J. S. et al., U.S. Pat. No.5,997,848). Pulmonary delivery has the advantage of administrationwithout needle injection, and obviates the need for potentially toxicpenetration enhancers.

[0234] Compositions suitable for use in the invention includecompositions wherein the active ingredients are contained in aneffective amount to achieve the intended purpose. The determination ofan effective dose is well within the capability of those skilled in theart.

[0235] Specialized forms of compositions may be prepared for directintracellular delivery of macromolecules comprising GCREC or fragmentsthereof. For example, liposome preparations containing acell-impermeable macromolecule may promote cell fusion and intracellulardelivery of the macromolecule. Alternatively, GCREC or a fragmentthereof may be joined to a short cationic N-terminal portion from theHIV Tat-1 protein. Fusion proteins thus generated have been found totransduce into the cells of all tissues, including the brain, in a mousemodel system (Schwarze, S. R. et al. (1999) Science 285:1569-1572).

[0236] For any compound, the therapeutically effective dose can beestimated initially either in cell culture assays, e.g., of neoplasticcells, or in animal models such as mice, rats, rabbits, dogs, monkeys,or pigs. An animal model may also be used to determine the appropriateconcentration range and route of administration. Such information canthen be used to determine useful doses and routes for administration inhumans.

[0237] A therapeutically effective dose refers to that amount of activeingredient, for example GCREC or fragments thereof, antibodies of GCREC,and agonists, antagonists or inhibitors of GCREC, which ameliorates thesymptoms or condition. Therapeutic efficacy and toxicity may bedetermined by standard pharmaceutical procedures in cell cultures orwith experimental animals, such as by calculating the ED₅₀ (the dosetherapeutically effective in 50% of the population) or LD₅₀ (the doselethal to 50% of the population) statistics. The dose ratio of toxic totherapeutic effects is the therapeutic index, which can be expressed asthe LD₅₀MD₅₀ ratio. Compositions which exhibit large therapeutic indicesare preferred. The data obtained from cell culture assays and animalstudies are used to formulate a range of dosage for human use. Thedosage contained in such compositions is preferably within a range ofcirculating concentrations that includes the ED₅₀ with little or notoxicity. The dosage varies within this range depending upon the dosageform employed, the sensitivity of the patient, and the route ofadministration.

[0238] The exact dosage will be determined by the practitioner, in lightof factors related to the subject requiring treatment. Dosage andadministration are adjusted to provide sufficient levels of the activemoiety or to maintain the desired effect. Factors which may be takeninto account include the severity of the disease state, the generalhealth of the subject, the age, weight, and gender of the subject, timeand frequency of administration, drug combination(s), reactionsensitivities, and response to therapy. Long-acting compositions may beadministered every 3 to 4 days, every week, or biweekly depending on thehalf-life and clearance rate of the particular formulation.

[0239] Normal dosage amounts may vary from about 0.1 μg to 100,000 μg,up to a total dose of about 1 gram, depending upon the route ofadministration. Guidance as to particular dosages and methods ofdelivery is provided in the literature and generally available topractitioners in the art. Those skilled in the art will employ differentformulations for nucleotides than for proteins or their inhibitors.Similarly, delivery of polynucleotides or polypeptides will be specificto particular cells, conditions, locations, etc.

[0240] Diagnostics

[0241] In another embodiment, antibodies which specifically bind GCRECmay be used for the diagnosis of disorders characterized by expressionof GCREC, or in assays to monitor patients being treated with GCREC oragonists, antagonists, or inhibitors of GCREC. Antibodies useful fordiagnostic purposes may be prepared in the same manner as describedabove for therapeutics. Diagnostic assays for GCREC include methodswhich utilize the antibody and a label to detect GCREC in human bodyfluids or in extracts of cells or tissues. The antibodies may be usedwith or without modification, and may be labeled by covalent ornon-covalent attachment of a reporter molecule. A wide variety ofreporter molecules, several of which are described above, are known inthe art and may be used.

[0242] A variety of protocols for measuring GCREC, including ELISAs,RIAs, and FACS, are known in the art and provide a basis for diagnosingaltered or abnormal levels of GCREC expression. Normal or standardvalues for GCREC expression are established by combining body fluids orcell extracts taken from normal mammalian subjects, for example, humansubjects, with antibodies to GCREC under conditions suitable for complexformation. The amount of standard complex formation may be quantitatedby various methods, such as photometric means. Quantities of GCRECexpressed in subject, control, and disease samples from biopsied tissuesare compared with the standard values. Deviation between standard andsubject values establishes the parameters for diagnosing disease.

[0243] In another embodiment of the invention, the polynucleotidesencoding GCREC may be used for diagnostic purposes. The polynucleotideswhich may be used include oligonucleotide sequences, complementary RNAand DNA molecules, and PNAs. The polynucleotides maybe used to detectand quantify gene expression in biopsied tissues in which expression ofGCREC may be correlated with disease. The diagnostic assay may be usedto determine absence, presence, and excess expression of GCREC, and tomonitor regulation of GCREC levels during therapeutic intervention.

[0244] In one aspect, hybridization with PCR probes which are capable ofdetecting polynucleotide sequences, including genomic sequences,encoding GCREC or closely related molecules may be used to identifynucleic acid sequences which encode GCREC. The specificity of the probe,whether it is made from a highly specific region, e.g., the 5′regulatory region, or from a less specific region, e.g., a conservedmotif, and the stringency of the hybridization or amplification willdetermine whether the probe identifies only naturally occurringsequences encoding GCREC, allelic variants, or related sequences.

[0245] Probes may also be used for the detection of related sequences,and may have at least 50% sequence identity to any of the GCREC encodingsequences. The hybridization probes of the subject invention may be DNAor RNA and may be derived from the sequence of SEQ ID NO:74-146 or fromgenomic sequences including promoters, enhancers, and introns of theGCREC gene.

[0246] Means for producing specific hybridization probes for DNAsencoding GCREC include the cloning of polynucleotide sequences encodingGCREC or GCREC derivatives into vectors for the production of mRNAprobes. Such vectors are known in the art, are commercially available,and may be used to synthesize RNA probes in vitro by means of theaddition of the appropriate RNA polymerases and the appropriate labelednucleotides. Hybridization probes may be labeled by a variety ofreporter groups, for example, by radionuclides such as ³²P or ³⁵S, or byenzymatic labels, such as alkaline phosphatase coupled to the probe viaavidin/biotin coupling systems, and the like.

[0247] Polynucleotide sequences encoding GCREC may be used for thediagnosis of disorders associated with expression of GCREC. Examples ofsuch disorders include, but are not limited to, a cell proliferativedisorder such as actinic keratosis, arteriosclerosis, atherosclerosis,bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD),myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera,psoriasis, primary thrombocythemia, and cancers includingadenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma,teratocarcinoma, and, in particular, cancers of the adrenal gland,bladder, bone, bone marrow, brain, breast, cervix, gall bladder,ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle,ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin,spleen, testis, thymus, thyroid, and uterus; a neurological disordersuch as epilepsy, ischemic cerebrovascular disease, stroke, cerebralneoplasms, Alzheimer's disease, Pick's disease, Huntington's disease,dementia, Parkinson's disease and other extrapyramidal disorders,amyotrophic lateral sclerosis and other motor neuron disorders,progressive neural muscular atrophy, retinitis pigmentosa, hereditaryataxias, multiple sclerosis and other demyelinating diseases, bacterialand viral meningitis, brain abscess, subdural empyema, epidural abscess,suppurative intracranial thrombophlebitis, myelitis and radiculitis,viral central nervous system disease, prion diseases including kuru,Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, nutritional and metabolic diseases of thenervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinalhemangioblastomatosis, encephalotrigeminal syndrome, mental retardationand other developmental disorders of the central nervous system,cerebral palsy, neuroskeletal disorders, autonomic nervous systemdisorders, cranial nerve disorders, spinal cord diseases, musculardystrophy and other neuromuscular disorders, peripheral nervous systemdisorders, dermatomyositis and polymyositis, inherited, metabolic,endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis,mental disorders including mood, anxiety, and schizophrenic disorders,seasonal affective disorder (SAD), akathesia, amnesia, catatonia,diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses,postherpetic neuralgia, Tourette's disorder, progressive supranuclearpalsy, corticobasal degeneration, and familial frontotemporal dementia;a cardiovascular disorder such as arteriovenous fistula,atherosclerosis, hypertension, vasculitis, Raynaud's disease, aneurysms,arterial dissections, varicose veins, thrombophlebitis andphlebothrombosis, vascular tumors, complications of thrombolysis,balloon angioplasty, vascular replacement, and coronary artery bypassgraft surgery, congestive heart failure, ischemic heart disease, anginapectoris, myocardial infarction, hypertensive heart disease,degenerative valvular heart disease, calcific aortic valve stenosis,congenitally bicuspid aortic valve, mitral annular calcification, mitralvalve prolapse, rheumatic fever and rheumatic heart disease, infectiveendocarditis, nonbacterial thrombotic endocarditis, endocarditis ofsystemic lupus erythematosus, carcinoid heart disease, cardiomyopathy,myocarditis, pericarditis, neoplastic heart disease, congenital heartdisease, and complications of cardiac transplantation; agastrointestinal disorder such as dysphagia, peptic esophagitis,esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia,indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis,gastroparesis, antral or pyloric edema, abdominal angina, pyrosis,gastroenteritis, intestinal obstruction, infections of the intestinaltract, peptic ulcer, cholelithiasis, cholecystitis, cholestasis,pancreatitis, pancreatic carcinoma, biliary tract disease, hepatitis,hyperbilirubinemia, cirrhosis, passive congestion of the liver,hepatoma, infectious colitis, ulcerative colitis, ulcerative proctitis,Crohn's disease, Whipple's disease, Mallory-Weiss syndrome, coloniccarcinoma, colonic obstruction, irritable bowel syndrome, short bowelsyndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquiredininunodeficiency syndrome (AIDS) enteropathy, jaundice, hepaticencephalopathy, hepatorenal syndrome, hepatic steatosis,hemochromatosis, Wilson's disease, alpha₁-antitrypsin deficiency, Reye'ssyndrome, primary sclerosing cholangitis, liver infarction, portal veinobstruction and thrombosis, centrilobular necrosis, peliosis hepatis,hepatic vein thrombosis, veno-occlusive disease, preeclampsia,eclampsia, acute fatty liver of pregnancy, intrahepatic cholestasis ofpregnancy, and hepatic tumors including nodular hyperplasias, adenomas,and carcinomas; an autoimmune/inflammatory disorder such as acquiredimmunodeficiency syndrome (AIDS), Addison's disease, adult respiratorydistress syndrome, allergies, ankylosing spondylitis, amyloidosis,anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmunethyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermaldystrophy (APECED), bronchitis, cholecystitis, contact dermatitis,Crohi's disease, atopic dermatitis, dermatomyositis, diabetes mellitus,emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosisfetalis, erythema nodosum, atrophic gastritis, glomerulonephritis,Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis,hypereosinophilia, irritable bowel syndrome, multiple sclerosis,myasthenia gravis, myocardial or pericardial inflammation,osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis,Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjögren'ssyndrome, systemic anaphylaxis, systemic lupus erythematosus, systemicsclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Wernersyndrome, complications of cancer, hemodialysis, and extracorporealcirculation, viral, bacterial, fungal, parasitic, protozoal, andhelminthic infections, and trauma; a metabolic disorder such asdiabetes, obesity, and osteoporosis; and an infection by a viral agentclassified as adenovirus, arenavirus, bunyavirus, calicivirus,coronavirus, filovirus, hepadnavirus, herpesvirus, flavivirus,orthomyxovirus, parvovirus, papovavirus, paramyxovirus, picornavirus,poxvirus, reovirus, retrovirus, rhabdovirus, and tongavirus. Thepolynucleotide sequences encoding GCREC may be used in Southern ornorthern analysis, dot blot, or other membrane-based technologies; inPCR technologies; in dipstick, pin, and multiformat ELISA-like assays;and in microarrays utilizing fluids or tissues from patients to detectaltered GCREC expression. Such qualitative or quantitative methods arewell known in the art.

[0248] In a particular aspect, the nucleotide sequences encoding GCRECmay be useful in assays that detect the presence of associateddisorders, particularly those mentioned above. The nucleotide sequencesencoding GCREC may be labeled by standard methods and added to a fluidor tissue sample from a patient under conditions suitable for theformation of hybridization complexes. After a suitable incubationperiod, the sample is washed and the signal is quantified and comparedwith a standard value. If the amount of signal in the patient sample issignificantly altered in comparison to a control sample then thepresence of altered levels of nucleotide sequences encoding GCREC in thesample indicates the presence of the associated disorder. Such assaysmay also be used to evaluate the efficacy of a particular therapeutictreatment regimen in animal studies, in clinical trials, or to monitorthe treatment of an individual patient.

[0249] In order to provide a basis for the diagnosis of a disorderassociated with expression of GCREC, a normal or standard profile forexpression is established. This may be accomplished by combining bodyfluids or cell extracts taken from normal subjects, either animal orhuman, with a sequence, or a fragment thereof, encoding GCREC, underconditions suitable for hybridization or amplification. Standardhybridization may be quantified by comparing the values obtained fromnormal subjects with values from an experiment in which a known amountof a substantially purified polynucleotide is used. Standard valuesobtained in this manner may be compared with values obtained fromsamples from patients who are symptomatic for a disorder. Deviation fromstandard values is used to establish the presence of a disorder.

[0250] Once the presence of a disorder is established and a treatmentprotocol is initiated, hybridization assays may be repeated on a regularbasis to determine if the level of expression in the patient begins toapproximate that which is observed in the normal subject. The resultsobtained from successive assays may be used to show the efficacy oftreatment over a period ranging from several days to months.

[0251] With respect to cancer, the presence of an abnormal amount oftranscript (either under- or overexpressed) in biopsied tissue from anindividual may indicate a predisposition for the development of thedisease, or may provide a means for detecting the disease prior to theappearance of actual clinical symptoms. A more definitive diagnosis ofthis type may allow health professionals to employ preventative measuresor aggressive treatment earlier thereby preventing the development orfurther progression of the cancer.

[0252] Additional diagnostic uses for oligonucleotides designed from thesequences encoding GCREC may involve the use of PCR. These oligomers maybe chemically synthesized, generated enzymatically, or produced invitro. Oligomers will preferably contain a fragment of a polynucleotideencoding GCREC, or a fragment of a polynucleotide complementary to thepolynucleotide encoding GCREC, and will be employed under optimizedconditions for identification of a specific gene or condition. Oligomersmay also be employed under less stringent conditions for detection orquantification of closely related DNA or RNA sequences.

[0253] In a particular aspect, oligonucleotide primers derived from thepolynucleotide sequences encoding GCREC may be used to detect singlenucleotide polymorphisms (SNPs). SNPs are substitutions, insertions anddeletions that are a frequent cause of inherited or acquired geneticdisease in humans. Methods of SNP detection include, but are not limitedto, single-stranded conformation polymorphism (SSCP) and fluorescentSSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from thepolynucleotide sequences encoding GCREC are used to amplify DNA usingthe polymerase chain reaction (PCR). The DNA may be derived, forexample, from diseased or normal tissue, biopsy samples, bodily fluids,and the like. SNPs in the DNA cause differences in the secondary andtertiary structures of PCR products in single-stranded form, and thesedifferences are detectable using gel electrophoresis in nondenaturinggels. In fSCCP, the oligonucleotide primers are fluorescently labeled,which allows detection of the amplimers in high-throughput equipmentsuch as DNA sequencing machines. Additionally, sequence databaseanalysis methods, termed in silico SNP (isSNP), are capable ofidentifying polymorphisms by comparing the sequence of individualoverlapping DNA fragments which assemble into a common consensussequence. These computer-based methods filter out sequence variationsdue to laboratory preparation of DNA and sequencing errors usingstatistical models and automated analyses of DNA sequence chromatograms.In the alternative, SNPs may be detected and characterized by massspectrometry using, for example, the high throughput MASSARRAY system(Sequenom, Inc., San Diego Calif.).

[0254] SNPs may be used to study the genetic basis of human disease. Forexample, at least 16 common SNPs have been associated withnon-insulin-dependent diabetes mellitus. SNPs are also useful forexamining differences in disease outcomes in monogenic disorders, suchas cystic fibrosis, sickle cell anemia, or chronic granulomatousdisease. For example, variants in the mannose-binding lectin, MBL2, havebeen shown to be correlated with deleterious pulmonary outcomes incystic fibrosis. SNPs also have utility in pharmacogenomics, theidentification of genetic variants that influence a patient's responseto a drug, such as life-threatening toxicity. For example, a variationin N-acetyl transferase is associated with a high incidence ofperipheral neuropathy in response to the anti-tuberculosis drugisoniazid, while a variation in the core promoter of the ALOX5 generesults in diminished clinical response to treatment with an anti-asthmadrug that targets the 5-lipoxygenase pathway. Analysis of thedistribution of SNPs in different populations is useful forinvestigating genetic drift, mutation, recombination, and selection, aswell as for tracing the origins of populations and their migrations.(Taylor, J. G. et al. (2001) Trends Mol. Med. 7:507-512; Kwok, P.-Y. andZ. Gu (1999) Mol. Med. Today 5:538-543; Nowotny, P. et al. (2001) Curr.Opin. Neurobiol. 11:637-641.)

[0255] Methods which may also be used to quantify the expression ofGCREC include radiolabeling or biotinylating nucleotides,coamplification of a control nucleic acid, and interpolating resultsfrom standard curves. (See, e.g., Melby, P. C. et al. (1993) J. Immunol.Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem.212:229-236.) The speed of quantitation of multiple samples may beaccelerated by running the assay in a high-throughput format where theoligomer or polynucleotide of interest is presented in various dilutionsand a spectrophotometric or colorimetric response gives rapidquantitation.

[0256] In further embodiments, oligonucleotides or longer fragmentsderived from any of the polynucleotide sequences described herein may beused as elements on a microarray. The microarray can be used intranscript imaging techniques which monitor the relative expressionlevels of large numbers of genes simultaneously as described below. Themicroarray may also be used to identify genetic variants, mutations, andpolymorphisms. This information may be used to determine gene function,to understand the genetic basis of a disorder, to diagnose a disorder,to monitor progression/regression of disease as a function of geneexpression, and to develop and monitor the activities of therapeuticagents in the treatment of disease. In particular, this information maybe used to develop a pharmacogenomic profile of a patient in order toselect the most appropriate and effective treatment regimen for thatpatient. For example, therapeutic agents which are highly effective anddisplay the fewest side effects may be selected for a patient based onhis/her pharmacogenomic profile.

[0257] In another embodiment, GCREC, fragments of GCREC, or antibodiesspecific for GCREC may be used as elements on a microarray. Themicroarray may be used to monitor or measure protein-proteininteractions, drug-target interactions, and gene expression profiles, asdescribed above.

[0258] A particular embodiment relates to the use of the polynucleotidesof the present invention to generate a transcript image of a tissue orcell type. A transcript image represents the global pattern of geneexpression by a particular tissue or cell type. Global gene expressionpatterns are analyzed by quantifying the number of expressed genes andtheir relative abundance under given conditions and at a given time.(See Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat.No. 5,840,484, expressly incorporated by reference herein.) Thus atranscript image may be generated by hybridizing the polynucleotides ofthe present invention or their complements to the totality oftranscripts or reverse transcripts of a particular tissue or cell type.In one embodiment, the hybridization takes place in high-throughputformat, wherein the polynucleotides of the present invention or theircomplements comprise a subset of a plurality of elements on amicroarray. The resultant transcript image would provide a profile ofgene activity.

[0259] Transcript images may be generated using transcripts isolatedfrom tissues, cell lines, biopsies, or other biological samples. Thetranscript image may thus reflect gene expression in vivo, as in thecase of a tissue or biopsy sample, or in vitro, as in the case of a cellline.

[0260] Transcript images which profile the expression of thepolynucleotides of the present invention may also be used in conjunctionwith in vitro model systems and preclinical evaluation ofpharmaceuticals, as well as toxicological testing of industrial andnaturally-occurring environmental compounds. All compounds inducecharacteristic gene expression patterns, frequently termed molecularfingerprints or toxicant signatures, which are indicative of mechanismsof action and toxicity (Nuwaysir, E. F. et al. (1999) Mol. Carcinog.24:153-159; Steiner, S. and N. L. Anderson (2000) Toxicol. Lett.112-113:467-471, expressly incorporated by reference herein). If a testcompound has a signature similar to that of a compound with knowntoxicity, it is likely to share those toxic properties. Thesefingerprints or signatures are most useful and refined when they containexpression information from a large number of genes and gene families.Ideally, a genome-wide measurement of expression provides the highestquality signature. Even genes whose expression is not altered by anytested compounds are important as well, as the levels of expression ofthese genes are used to normalize the rest of the expression data. Thenormalization procedure is useful for comparison of expression dataafter treatment with different compounds. While the assignment of genefunction to elements of a toxicant signature aids in interpretation oftoxicity mechanisms, knowledge of gene function is not necessary for thestatistical matching of signatures which leads to prediction oftoxicity. (See, for example, Press Release 00-02 from the NationalInstitute of Environmental Health Sciences, released Feb. 29, 2000,available at http://www.niehs.nlh.gov/oc/news/toxchip.htm.) Therefore,it is important and desirable in toxicological screening using toxicantsignatures to include all expressed gene sequences.

[0261] In one embodiment, the toxicity of a test compound is assessed bytreating a biological sample containing nucleic acids with the testcompound. Nucleic acids that are expressed in the treated biologicalsample are hybridized with one or more probes specific to thepolynucleotides of the present invention, so that transcript levelscorresponding to the polynucleotides of the present invention may bequantified. The transcript levels in the treated biological sample arecompared with levels in an untreated biological sample. Differences inthe transcript levels between the two samples are indicative of a toxicresponse caused by the test compound in the treated sample.

[0262] Another particular embodiment relates to the use of thepolypeptide sequences of the present invention to analyze the proteomeof a tissue or cell type. The term proteome refers to the global patternof protein expression in a particular tissue or cell type. Each proteincomponent of a proteome can be subjected individually to furtheranalysis. Proteome expression patterns, or profiles, are analyzed byquantifying the number of expressed proteins and their relativeabundance under given conditions and at a given time. A profile of acell's proteome may thus be generated by separating and analyzing thepolypeptides of a particular tissue or cell type. In one embodiment, theseparation is achieved using two-dimensional gel electrophoresis, inwhich proteins from a sample are separated by isoelectric focusing inthe first dimension, and then according to molecular weight by sodiumdodecyl sulfate slab gel electrophoresis in the second dimension(Steiner and Anderson, supra). The proteins are visualized in the gel asdiscrete and uniquely positioned spots, typically by staining the gelwith an agent such as Coomassie Blue or silver or fluorescent stains.The optical density of each protein spot is generally proportional tothe level of the protein in the sample. The optical densities ofequivalently positioned protein spots from different samples, forexample, from biological samples either treated or untreated with a testcompound or therapeutic agent, are compared to identify any changes inprotein spot density related to the treatment. The proteins in the spotsare partially sequenced using, for example, standard methods employingchemical or enzymatic cleavage followed by mass spectrometry. Theidentity of the protein in a spot may be determined by comparing itspartial sequence, preferably of at least 5 contiguous amino acidresidues, to the polypeptide sequences of the present invention. In somecases, further sequence data may be obtained for definitive proteinidentification.

[0263] A proteomic profile may also be generated using antibodiesspecific for GCREC to quantify the levels of GCREC expression. In oneembodiment, the antibodies are used as elements on a microarray, andprotein expression levels are quantified by exposing the microarray tothe sample and detecting the levels of protein bound to each arrayelement (Lueking, A. et al. (1999) Anal. Biochem. 270:103-111;Mendoze,L. G. et al. (1999) Biotechniques 27:778-788). Detection may beperformed by a variety of methods known in the art, for example, byreacting the proteins in the sample with a thiol- or amino-reactivefluorescent compound and detecting the amount of fluorescence bound ateach array element.

[0264] Toxicant signatures at the proteome level are also useful fortoxicological screening, and should be analyzed in parallel withtoxicant signatures at the transcript level. There is a poor correlationbetween transcript and protein abundances for some proteins in sometissues (Anderson, N. L. and J. Seilhamer (1997) Electrophoresis18:533-537), so proteome toxicant signatures may be useful in theanalysis of compounds which do not significantly affect the transcriptimage, but which alter the proteomic profile. In addition, the analysisof transcripts in body fluids is difficult, due to rapid degradation ofmRNA, so proteomic profiling may be more reliable and informative insuch cases.

[0265] In another embodiment, the toxicity of a test compound isassessed by treating a biological sample containing proteins with thetest compound. Proteins that are expressed in the treated biologicalsample are separated so that the amount of each protein can bequantified. The amount of each protein is compared to the amount of thecorresponding protein in an untreated biological sample. A difference inthe amount of protein between the two samples is indicative of a toxicresponse to the test compound in the treated sample. Individual proteinsare identified by sequencing the amino acid residues of the individualproteins and comparing these partial sequences to the polypeptides ofthe present invention.

[0266] In another embodiment, the toxicity of a test compound isassessed by treating a biological sample containing proteins with thetest compound. Proteins from the biological sample are incubated withantibodies specific to the polypeptides of the present invention. Theamount of protein recognized by the antibodies is quantified. The amountof protein in the treated biological sample is compared with the amountin an untreated biological sample. A difference in the amount of proteinbetween the two samples is indicative of a toxic response to the testcompound in the treated sample.

[0267] Microarrays may be prepared, used, and analyzed using methodsknown in the art. (See, e.g., Brennan, T. M. et al. (1995) U.S. Pat. No.5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA93:10614-10619; Baldeschweiler et al. (1995) PCT applicationWO95/251116; Shalon, D. et al. (1995) PCT application WO95/35505;Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; andHeller, M. J. et al. (1997) U.S. Pat. No. 5,605,662.) Various types ofmicroarrays are well known and thoroughly described in DNA Microarrays:A Practical Approach, M. Schena, ed. (1999) Oxford University Press,London, hereby expressly incorporated by reference.

[0268] In another embodiment of the invention, nucleic acid sequencesencoding GCREC may be used to generate hybridization probes useful inmapping the naturally occurring genomic sequence. Either coding ornoncoding sequences may be used, and in some instances, noncodingsequences may be preferable over coding sequences. For example,conservation of a coding sequence among members of a multi-gene familymay potentially cause undesired cross hybridization during chromosomalmapping. The sequences may be mapped to a particular chromosome, to aspecific region of a chromosome, or to artificial chromosomeconstructions, e.g., human artificial chromosomes (HACs), yeastartificial chromosomes (YACs), bacterial artificial chromosomes (BACs),bacterial P1 constructions, or single chromosome cDNA libraries. (See,e.g., Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355; Price, C.M. (1993) Blood Rev. 7:127-134; and Trask, B. J. (1991) Trends Genet.7:149-154.) Once mapped, the nucleic acid sequences of the invention maybe used to develop genetic linkage maps, for example, which correlatethe inheritance of a disease state with the inheritance of a particularchromosome region or restriction fragment length polymorphism (RLFP).(See, for example, Lander, E. S. and D. Botstein (1986) Proc. Natl.Acad. Sci. USA 83:7353-7357.)

[0269] Fluorescent in situ hybridization (FISH) may be correlated withother physical and genetic map data. (See, e.g., Heinz-Ulrich, et al.(1995) in Meyers, supra, pp. 965-968.) Examples of genetic map data canbe found in various scientific journals or at the Online MendelianInheritance in Man (OMIM) World Wide Web site. Correlation between thelocation of the gene encoding GCREC on a physical map and a specificdisorder, or a predisposition to a specific disorder, may help definethe region of DNA associated with that disorder and thus may furtherpositional cloning efforts.

[0270] In situ hybridization of chromosomal preparations and physicalmapping techniques, such as linkage analysis using establishedchromosomal markers, may be used for extending genetic maps. Often theplacement of a gene on the chromosome of another mammalian species, suchas mouse, may reveal associated markers even if the exact chromosomallocus is not known. This information is valuable to investigatorssearching for disease genes using positional cloning or other genediscovery techniques. Once the gene or genes responsible for a diseaseor syndrome have been crudely localized by genetic linkage to aparticular genomic region, e.g., ataxia-telangiectasia to 11q22-23, anysequences mapping to that area may represent associated or regulatorygenes for further investigation. (See, e.g., Gatti, R. A. et al. (1988)Nature 336:577-580.) The nucleotide sequence of the instant inventionmay also be used to detect differences in the chromosomal location dueto translocation, inversion, etc., among normal, carrier, or affectedindividuals.

[0271] In another embodiment of the invention, GCREC, its catalytic orimmunogenic fragments, or oligopeptides thereof can be used forscreening libraries of compounds in any of a variety of drug screeningtechniques. The fragment employed in such screening may be free insolution, affixed to a solid support, borne on a cell surface, orlocated intracellularly. The formation of binding complexes betweenGCREC and the agent being tested may be measured.

[0272] Another technique for drug screening provides for high throughputscreening of compounds having suitable binding affinity to the proteinof interest. (See, e.g., Geysen, et al. (1984) PCT applicationWO84/03564.) In this method, large numbers of different small testcompounds are synthesized on a solid substrate. The test compounds arereacted with GCREC, or fragments thereof, and washed. Bound GCREC isthen detected by methods well known in the art. Purified GCREC can alsobe coated directly onto plates for use in the aforementioned drugscreening techniques. Alternatively, non-neutralizing antibodies can beused to capture the peptide and immobilize it on a solid support.

[0273] In another embodiment, one may use competitive drug screeningassays in which neutralizing antibodies capable of binding GCRECspecifically compete with a test compound for binding GCREC. In thismanner, antibodies can be used to detect the presence of any peptidewhich shares one or more antigenic determinants with GCREC.

[0274] In additional embodiments, the nucleotide sequences which encodeGCREC may be used in any molecular biology techniques that have yet tobe developed, provided the new techniques rely on properties ofnucleotide sequences that are currently known, including, but notlimited to, such properties as the triplet genetic code and specificbase pair interactions.

[0275] Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, utilize the presentinvention to its fullest extent. The following embodiments are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever.

[0276] Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, utilize the presentinvention to its fullest extent. The following preferred specificembodiments are, therefore, to be construed as merely illustrative, andnot limitative of the remainder of the disclosure in any way whatsoever.

[0277] The disclosures of all patents, applications, and publicationsmentioned above and below, including U.S. Ser. No. 60/280,683, U.S. Ser.No. 60/283,714, U.S. Ser. No. 60/287,266, and U.S. Ser. No. 60/285,336,are hereby expressly incorporated by reference.

EXAMPLES

[0278] I. Construction of cDNA Libraries

[0279] Incyte cDNAs were derived from cDNA libraries described in theLIFESEQ GOLD database (Incyte Genomics, Palo Alto Calif.). Some tissueswere homogenized and lysed in guanidinium isothiocyanate, while otherswere homogenized and lysed in phenol or in a suitable mixture ofdenaturants, such as TRIZOL (Life Technologies), a monophasic solutionof phenol and guanidine isothiocyanate. The resulting lysates werecentrifuged over CsCl cushions or extracted with chloroform. RNA wasprecipitated from the lysates with either isopropanol or sodium acetateand ethanol, or by other routine methods.

[0280] Phenol extraction and precipitation of RNA were repeated asnecessary to increase RNA purity. In some cases, RNA was treated withDNase. For most libraries, poly(A)+ RNA was isolated using oligod(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles(QIAGEN, Chatsworth Calif.), or an OLIGOTEX mRNA purification kit(QIAGEN). Alternatively, RNA was isolated directly from tissue lysatesusing other RNA isolation kits, e.g., the POLY(A)PURE mRNA purificationkit (Ambion, Austin Tex.).

[0281] In some cases, Stratagene was provided with RNA and constructedthe corresponding cDNA libraries. Otherwise, cDNA was synthesized andcDNA libraries were constructed with the UNIZAP vector system(Stratagene) or SUPERSCRIPT plasmid system (Life Technologies), usingthe recommended procedures or similar methods known in the art. (See,e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription wasinitiated using oligo d(T) or random primers. Synthetic oligonucleotideadapters were ligated to double stranded cDNA, and the cDNA was digestedwith the appropriate restriction enzyme or enzymes. For most libraries,the cDNA was size-selected (300-1000 bp) using SEPHACRYL S1000,SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (AmershamPharmacia Biotech) or preparative agarose gel electrophoresis. cDNAswere ligated into compatible restriction enzyme sites of the polylinkerof a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1plasmid (Life Technologies), PCDNA2.1 plasmid (Invitrogen, CarlsbadCalif.), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen),PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte Genomics, Palo AltoCalif.), pRARE (Incyte Genomics), or pINCY (Incyte Genomics), orderivatives thereof. Recombinant plasmids were transformed intocompetent E. coli cells including XL1-Blue, XLl-BlueMRF, or SOLR fromStratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies.

[0282] II. Isolation of cDNA Clones

[0283] Plasmids obtained as described in Example I were recovered fromhost cells by in vivo excision using the UNIZAP vector system(Stratagene) or by cell lysis. Plasmids were purified using at least oneof the following: a Magic or WIZARD Minipreps DNA purification system(Promega); an AGTC Miniprep purification kit (Edge Biosystems,Gaithersburg Md.); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid,QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96plasmid purification kit from QIAGEN. Following precipitation, plasmidswere resuspended in 0.1 ml of distilled water and stored, with orwithout lyophilization, at 4° C.

[0284] Alternatively, plasmid DNA was amplified from host cell lysatesusing direct link PCR in a high-throughput format (Rao, V. B. (1994)Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps werecarried out in a single reaction mixture. Samples were processed andstored in 384-well plates, and the concentration of amplified plasmidDNA was quantified fluorometrically using PICOGREEN dye (MolecularProbes, Eugene Oreg.) and a FLUOROSKAN II fluorescence scanner(Labsystems Oy, Helsinki, Finland).

[0285] III. Sequencing and Analysis

[0286] Incyte cDNA recovered in plasmids as described in Example II weresequenced as follows. Sequencing reactions were processed using standardmethods or high-throughput instrumentation such as the ABI CATALYST 800(Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJResearch) in conjunction with the HYDRA microdispenser (RobbinsScientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNAsequencing reactions were prepared using reagents provided by AmershamPharmacia Biotech or supplied in ABI sequencing kits such as the ABIPRISM BIGDYE Terminator cycle sequencing ready reaction kit (AppliedBiosystems). Electrophoretic separation of cDNA sequencing reactions anddetection of labeled polynucleotides were carried out using the MEGABACE1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or377 sequencing system (Applied Biosystems) in conjunction with standardABI protocols and base calling software; or other sequence analysissystems known in the art. Reading frames within the cDNA sequences wereidentified using standard methods (reviewed in Ausubel, 1997, supra,unit 7.7). Some of the cDNA sequences were selected for extension usingthe techniques disclosed in Example VIII.

[0287] The polynucleotide sequences derived from Incyte cDNAs werevalidated by removing vector, linker, and poly(A) sequences and bymasking ambiguous bases, using algorithms and programs based on BLAST,dynamic programming, and dinucleotide nearest neighbor analysis. TheIncyte cDNA sequences or translations thereof were then queried againsta selection of public databases such as the GenBank primate, rodent,mammalian, vertebrate, and eukaryote databases, and BLOCKS, PRINTS,DOMO, PRODOM; PROTEOME databases with sequences from Homo sapiens,Rattus norvegicus, Mus musculus, Caenorhabditis elegans, Saccharomycescerevisiae, Schizosaccharomvces pombe, and Candida albicans (IncyteGenomics, Palo Alto Calif.); hidden Markov model (HMM)-based proteinfamily databases such as PFAM, INCY, and TIGRFAM (Haft, D. H. et al.(2001) Nucleic Acids Res. 29:41-43); and HMM-based protein domaindatabases such as SMART (Schultz et al. (1998) Proc. Natl. Acad. Sci.USA 95:5857-5864; Letunic, I. et al. (2002) Nucleic Acids Res.30:242-244). (HMM is a probabilistic approach which analyzes consensusprimary structures of gene families. See, for example, Eddy, S. R.(1996) Curr. Opin. Struct. Biol. 6:361-365.) The queries were performedusing programs based on BLAST, FASTA, BUMPS, and HMMER. The Incyte cDNAsequences were assembled to produce full length polynucleotidesequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitchedsequences, stretched sequences, or Genscan-predicted coding sequences(see Examples IV and V) were used to extend Incyte cDNA assemblages tofull length. Assembly was performed using programs based on Phred,Phrap, and Consed, and cDNA assemblages were screened for open readingframes using programs based on GeneMark, BLAST, and FASTA. The fulllength polynucleotide sequences were translated to derive thecorresponding full length polypeptide sequences. Alternatively, apolypeptide of the invention may begin at any of the methionine residuesof the full length translated polypeptide. Full length polypeptidesequences were subsequently analyzed by querying against databases suchas the GenBank protein databases (genpept), SwissProt, the PROTEOMEdatabases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, hidden Markov model(HMM)-based protein family databases such as PFAM, INCY, and TIGRFAM;and HMM-based protein domain databases such as SMART. Full lengthpolynucleotide sequences are also analyzed using MACDNASIS PRO software(Hitachi Software Engineering, South San Francisco Calif.) and LASERGENEsoftware (DNASTAR). Polynucleotide and polypeptide sequence alignmentsare generated using default parameters specified by the CLUSTALalgorithm as incorporated into the MEGALIGN multisequence alignmentprogram (DNASTAR), which also calculates the percent identity betweenaligned sequences.

[0288] Table 7 summarizes the tools, programs, and algorithms used forthe analysis and assembly of Incyte cDNA and full length sequences andprovides applicable descriptions, references, and threshold parameters.The first column of Table 7 shows the tools, programs, and algorithmsused, the second column provides brief descriptions thereof, the thirdcolumn presents appropriate references, all of which are incorporated byreference herein in their entirety, and the fourth column presents,where applicable, the scores, probability values, and other parametersused to evaluate the strength of a match between two sequences (thehigher the score or the lower the probability value, the greater theidentity between two sequences).

[0289] The programs described above for the assembly and analysis offull length polynucleotide and polypeptide sequences were also used toidentify polynucleotide sequence fragments from SEQ ID NO:74-146.Fragments from about 20 to about 4000 nucleotides which are useful inhybridization and amplification technologies are described in Table 4,column 2.

[0290] IV. Identification and Editing of Coding Sequences from GenomicDNA

[0291] Putative G-protein coupled receptors were initially identified byrunning the Genscan gene identification program against public genomicsequence databases (e.g., gbpri and gbhtg). Genscan is a general-purposegene identification program which analyzes genomic DNA sequences from avariety of organisms (See Burge, C. and S. Karlin (1997) J. Mol. Biol.268:78-94, and Burge, C. and S. Karlin (1998) Curr. Opin. Struct. Biol.8:346-354). The program concatenates predicted exons to form anassembled cDNA sequence extending from a methionine to a stop codon. Theoutput of Genscan is a FASTA database of polynucleotide and polypeptidesequences. The maximum range of sequence for Genscan to analyze at oncewas set to 30 kb. To determine which of these Genscan predicted cDNAsequences encode G-protein coupled receptors, the encoded polypeptideswere analyzed by querying against PFAM models for G-protein coupledreceptors. Potential G-protein coupled receptors were also identified byhomology to Incyte cDNA sequences that had been annotated as G-proteincoupled receptors. These selected Genscan-predicted sequences were thencompared by BLAST analysis to the genpept and gbpri public databases.Where necessary, the Genscan-predicted sequences were then edited bycomparison to the top BLAST hit from genpept to correct errors in thesequence predicted by Genscan, such as extra or omitted exons. BLASTanalysis was also used to find any Incyte cDNA or public cDNA coverageof the Genscan-predicted sequences, thus providing evidence fortranscription. When Incyte cDNA coverage was available, this informationwas used to correct or confirm the Genscan predicted sequence. Fulllength polynucleotide sequences were obtained by assemblingGenscan-predicted coding sequences with Incyte cDNA sequences and/orpublic cDNA sequences using the assembly process described in ExampleIII. Alternatively, full length polynucleotide sequences were derivedentirely from edited or unedited Genscan-predicted coding sequences.

[0292] V. Assembly of Genomic Sequence Data with cDNA Sequence Data

[0293] “Stitched” Sequences

[0294] Partial cDNA sequences were extended with exons predicted by theGenscan gene identification program described in Example IV. PartialcDNAs assembled as described in Example III were mapped to genomic DNAand parsed into clusters containing related cDNAs and Genscan exonpredictions from one or more genomic sequences. Each cluster wasanalyzed using an algorithm based on graph theory and dynamicprogramming to integrate cDNA and genomic information, generatingpossible splice variants that were subsequently confirmed, edited, orextended to create a full length sequence. Sequence intervals in whichthe entire length of the interval was present on more than one sequencein the cluster were identified, and intervals thus identified wereconsidered to be equivalent by transitivity. For example, if an intervalwas present on a cDNA and two genomic sequences, then all threeintervals were considered to be equivalent. This process allowsunrelated but consecutive genomic sequences to be brought together,bridged by cDNA sequence. Intervals thus identified were then “stitched”together by the stitching algorithm in the order that they appear alongtheir parent sequences to generate the longest possible sequence, aswell as sequence variants. Linkages between intervals which proceedalong one type of parent sequence (cDNA to cDNA or genomic sequence togenomic sequence) were given preference over linkages which changeparent type (cDNA to genomic sequence). The resultant stitched sequenceswere translated and compared by BLAST analysis to the genpept and gbpripublic databases. Incorrect exons predicted by Genscan were corrected bycomparison to the top BLAST hit from genpept. Sequences were furtherextended with additional cDNA sequences, or by inspection of genornicDNA, when necessary.

[0295] “Stretched” Sequences

[0296] Partial DNA sequences were extended to full length with analgorithm based on BLAST analysis. First, partial cDNAs assembled asdescribed in Example m were queried against public databases such as theGenBank primate, rodent, mammalian, vertebrate, and eukaryote databasesusing the BLAST program. The nearest GenBank protein homolog was thencompared by BLAST analysis to either Incyte cDNA sequences or GenScanexon predicted sequences described in Example IV. A chimeric protein wasgenerated by using the resultant high-scoring segment pairs (HSPs) tomap the translated sequences onto the GenBank protein homolog.Insertions or deletions may occur in the chimeric protein with respectto the original GenBank protein homolog. The GenBank protein homolog,the chimeric protein, or both were used as probes to search forhomologous genomic sequences from the public human genome databases.Partial DNA sequences were therefore “stretched” or extended by theaddition of homologous genomic sequences. The resultant stretchedsequences were examined to determine whether it contained a completegene.

[0297] VI. Chromosomal Mapping of GCREC Encoding Polynucleotides

[0298] The sequences which were used to assemble SEQ ID NO:74-146 werecompared with sequences from the Incyte LIFESEQ database and publicdomain databases using BLAST and other implementations of theSmith-Waterman algorithm. Sequences from these databases that matchedSEQ ID NO:74-146 were assembled into clusters of contiguous andoverlapping sequences using assembly algorithms such as Phrap (Table 7).Radiation hybrid and genetic mapping data available from publicresources such as the Stanford Human Genome Center (SHGC), WhiteheadInstitute for Genome Research (WIGR), and Genethon were used todetermine if any of the clustered sequences had been previously mapped.Inclusion of a mapped sequence in a cluster resulted in the assignmentof all sequences of that cluster, including its particular SEQ ID NO:,to that map location.

[0299] Map locations are represented by ranges, or intervals, of humanchromosomes. The map position of an interval, in centiMorgans, ismeasured relative to the terminus of the chromosome's p-arm. (ThecentiMorgan (cM) is a unit of measurement based on recombinationfrequencies between chromosomal markers. On average, 1 cM is roughlyequivalent to 1 megabase (Mb) of DNA in humans, although this can varywidely due to hot and cold spots of recombination.) The cM distances arebased on genetic markers mapped by Genethon which provide boundaries forradiation hybrid markers whose sequences were included in each of theclusters. Human genome maps and other resources available to the public,such as the NCB1 “GeneMap'99” World Wide Web site(http://www.ncbi.nlm.nlh.gov/genemap/), can be employed to determine ifpreviously identified disease genes map within or in proximity to theintervals indicated above.

[0300] VII. Analysis of Polynucleotide Expression

[0301] Northern analysis is a laboratory technique used to detect thepresence of a transcript of a gene and involves the hybridization of alabeled nucleotide sequence to a membrane on which RNAs from aparticular cell type or tissue have been bound. (See, e.g., Sambrook,supra, ch. 7; Ausubel (1995) supra, ch. 4 and 16.)

[0302] Analogous computer techniques applying BLAST were used to searchfor identical or related molecules in cDNA databases such as GenBank orLIFESEQ (Incyte Genomics). This analysis is much faster than multiplemembrane-based hybridizations. In addition, the sensitivity of thecomputer search can be modified to determine whether any particularmatch is categorized as exact or similar. The basis of the search is theproduct score, which is defined as:$\frac{{BLAST}\quad {Score} \times {Percent}\quad {Identity}}{5 \times {minimum}\quad \left\{ {{{length}\left( {{Seq}.\quad 1} \right)},{{length}\left( {{Seq}.\quad 2} \right)}} \right\}}$

[0303] The product score takes into account both the degree ofsimilarity between two sequences and the length of the sequence match.The product score is a normalized value between 0 and 100, and iscalculated as follows: the BLAST score is multiplied by the percentnucleotide identity and the product is divided by (5 times the length ofthe shorter of the two sequences). The BLAST score is calculated byassigning a score of +5 for every base that matches in a high-scoringsegment pair (HSP), and −4 for every mismatch. Two sequences may sharemore than one HSP (separated by gaps). If there is more than one HSP,then the pair with the highest BLAST score is used to calculate theproduct score. The product score represents a balance between fractionaloverlap and quality in a BLAST alignment. For example, a product scoreof 100 is produced only for 100% identity over the entire length of theshorter of the two sequences being compared. A product score of 70 isproduced either by 100% identity and 70% overlap at one end, or by 88%identity and 100% overlap at the other. A product score of 50 isproduced either by 100% identity and 50% overlap at one end, or 79%identity and 100% overlap.

[0304] Alternatively, polynucleotide sequences encoding GCREC areanalyzed with respect to the tissue sources from which they werederived. For example, some full length sequences are assembled, at leastin part, with overlapping Incyte cDNA sequences (see Example III). EachcDNA sequence is derived from a cDNA library constructed from a humantissue. Each human tissue is classified into one of the followingorgan/tissue categories: cardiovascular system; connective tissue;digestive system; embryonic structures; endocrine system; exocrineglands; genitalia, female; genitalia, male; germ cells; hemic and immunesystem; liver; musculoskeletal system; nervous system; pancreas;respiratory system; sense organs; skin; stomatognathic system;unclassified/mixed; or urinary tract. The number of libraries in eachcategory is counted and divided by the total number of libraries acrossall categories. Similarly, each human tissue is classified into one ofthe following disease/condition categories: cancer, cell line,developmental, inflammation, neurological, trauma, cardiovascular,pooled, and other, and the number of libraries in each category iscounted and divided by the total number of libraries across allcategories. The resulting percentages reflect the tissue- anddisease-specific expression of cDNA encoding GCREC. cDNA sequences andcDNA library/tissue information are found in the LIFESEQ GOLD database(Incyte Genomics, Palo Alto Calif.).

[0305] VIII. Extension of GCREC Encoding Polynucleotides

[0306] Full length polynucleotide sequences were also produced byextension of an appropriate fragment of the full length molecule usingoligonucleotide primers designed from this fragment. One primer wassynthesized to initiate 5′ extension of the known fragment, and theother primer was synthesized to initiate 3′ extension of the knownfragment. The initial primers were designed using OLIGO 4.06 software(National Biosciences), or another appropriate program, to be about 22to 30 nucleotides in length, to have a GC content of about 50% or more,and to anneal to the target sequence at temperatures of about 68° C. toabout 72° C. Any stretch of nucleotides which would result in hairpinstructures and primer-primer dimerizations was avoided.

[0307] Selected human cDNA libraries were used to extend the sequence.If more than one extension was necessary or desired, additional ornested sets of primers were designed.

[0308] High fidelity amplification was obtained by PCR using methodswell known in the art. PCR was performed in 96-well plates using thePTC-200 thermal cycler (MJ Research, Inc.). The reaction mix containedDNA template, 200 nmol of each primer, reaction buffer containing Mg²⁺,(NH₄)₂SO₄, and 2-mercaptoethanol, Taq DNA polymerase (Amersham PharmaciaBiotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase(Stratagene), with the following parameters for primer pair PCI A andPCI B: Step 1: 94° C., 3 min; Step 2: 94° C., 15 sec; Step 3: 60° C., 1min; Step 4: 68° C., 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times;Step 6: 68° C., 5 min; Step 7: storage at 4° C. In the alternative, theparameters for primer pair T7 and SK+ were as follows: Step 1: 94° C., 3min; Step 2: 94° C., 15 sec; Step 3: 57° C., 1 min; Step 4: 68° C., 2min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68° C., 5 min;Step 7: storage at 4° C.

[0309] The concentration of DNA in each well was determined bydispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN;Molecular Probes, Eugene Oreg.) dissolved in 1×TE and 0.5 μl ofundiluted PCR product into each well of an opaque fluorimeter plate(Corning Costar, Acton Mass.), allowing the DNA to bind to the reagentThe plate was scanned in a Fluoroskan II (Labsystems Oy, Helsinki,Finland) to measure the fluorescence of the sample and to quantify theconcentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixturewas analyzed by electrophoresis on a 1% agarose gel to determine whichreactions were successful in extending the sequence.

[0310] The extended nucleotides were desalted and concentrated,transferred to 384-well plates, digested with CviJI cholera virusendonuclease (Molecular Biology Research, Madison Wis.), and sonicatedor sheared prior to religation into pUC 18 vector (Amersham PharmaciaBiotech). For shotgun sequencing, the digested nucleotides wereseparated on low concentration (0.6 to 0.8%) agarose gels, fragmentswere excised, and agar digested with Agar ACE (Promega). Extended cloneswere religated using T4 ligase (New England Biolabs, Beverly Mass.) intopUC 18 vector (Amersham Pharmacia Biotech), treated with Pfu DNApolymerase (Stratagene) to fill-in restriction site overhangs, andtransfected into competent E. coli cells. Transformed cells wereselected on antibiotic-containing media, and individual colonies werepicked and cultured overnight at 37° C. in 384-well plates in LB/2×carbliquid media.

[0311] The cells were lysed, and DNA was amplified by PCR using Taq DNApolymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase(Stratagene) with the following parameters: Step 1: 94° C., 3 min; Step2: 94° C., 15 sec; Step 3: 60° C., 1 min; Step 4: 72° C., 2 min; Step 5:steps 2, 3, and 4 repeated 29 times; Step 6: 72° C., 5 min; Step 7:storage at 4° C. DNA was quantified by PICOGREEN reagent (MolecularProbes) as described above. Samples with low DNA recoveries werereamplified using the same conditions as described above. Samples werediluted with 20% dimethysulfoxide (1:2, v/v), and sequenced usingDYENAMIC energy transfer sequencing primers and the DYENAMC DIRECT kit(Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cyclesequencing ready reaction kit (Applied Biosystems).

[0312] In like manner, full length polynucleotide sequences are verifiedusing the above procedure or are used to obtain 5′ regulatory sequencesusing the above procedure along with oligonucleotides designed for suchextension, and an appropriate genomic library.

[0313] IX. Identification of Single Nucleotide Polymorphisms in GCRECEncoding Polynucleotides

[0314] Common DNA sequence variants known as single nucleotidepolymorphisms (SNPs) were identified in SEQ ID NO:74-146 using theLFESEQ database (Incyte Genomics). Sequences from the same gene wereclustered together and assembled as described in Example III, allowingthe identification of all sequence variants in the gene. An algorithmconsisting of a series of filters was used to distinguish SNPs fromother sequence variants. Preliminary filters removed the majority ofbasecall errors by requiring a minimum Phred quality score of 15, andremoved sequence alignment errors and errors resulting from impropertrimming of vector sequences, chimeras, and splice variants. Anautomated procedure of advanced chromosome analysis analysed theoriginal chromatogram files in the vicinity of the putative SNP. Cloneerror filters used statistically generated algorithms to identify errorsintroduced during laboratory processing, such as those caused by reversetranscriptase, polymerase, or somatic mutation. Clustering error filtersused statistically generated algorithms to identify errors resultingfrom clustering of close homologs or pseudogenes, or due tocontamination by non-human sequences. A final set of filters removedduplicates and SNPs found in immunoglobulins or T-cell receptors.

[0315] Certain SNPs were selected for further characterization by massspectrometry using the high throughput MASSARRAY system (Sequenom, Inc.)to analyze allele frequencies at the SNP sites in four different humanpopulations. The Caucasian population comprised 92 individuals (46 male,46 female), including 83 from Utah, four French, three Venezualan, andtwo Amish individuals. The African population comprised 194 individuals(97 male, 97 female), all African Americans. The Hispanic populationcomprised 324 individuals (162 male, 162 female), all Mexican Hispanic.The Asian population comprised 126 individuals (64 male, 62 female) witha reported parental breakdown of 43% Chinese, 31% Japanese, 13% Korean,5% Vietnamese, and 8% other Asian. Allele frequencies were firstanalyzed in the Caucasian population; in some cases those SNPs whichshowed no allelic variance in this population were not further tested inthe other three populations.

[0316] X. Labeling and Use of Individual Hybridization Probes

[0317] Hybridization probes derived from SEQ ID NO:74-146 are employedto screen cDNAs, genomic DNAs, or mRNAs. Although the labeling ofoligonucleotides, consisting of about 20 base pairs, is specificallydescribed, essentially the same procedure is used with larger nucleotidefragments. Oligonucleotides are designed using state-of-the-art softwaresuch as OLIGO 4.06 software (National Biosciences) and labeled bycombining 50 pmol of each oligomer, 250 μCi of [γ_(—) ³²P] adenosinetriphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase(DuPont NEN, Boston Mass.). The labeled oligonucleotides aresubstantially purified using a SEPHADEX G-25 superfine size exclusiondextran bead column (Amersham Pharmacia Biotech). An aliquot containing10⁷ counts per minute of the labeled probe is used in a typicalmembrane-based hybridization analysis of human genomic DNA digested withone of the following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I,or Pvu I (DuPont NEN).

[0318] The DNA from each digest is fractionated on a 0.7% agarose geland transferred to nylon membranes (Nytran Plus, Schleicher & Schuell,Durham N.H.). Hybridization is carried out for 16 hours at 40° C. Toremove nonspecific signals, blots are sequentially washed at roomtemperature under conditions of up to, for example, 0.1×saline sodiumcitrate and 0.5% sodium dodecyl sulfate. Hybridization patterns arevisualized using autoradiography or an alternative imaging means andcompared.

[0319] XI. Microarrays

[0320] The linkage or synthesis of array elements upon a microarray canbe achieved utilizing photolithography, piezoelectric printing (ink-jetprinting, See, e.g., Baldeschweiler, supra.), mechanical microspottingtechnologies, and derivatives thereof. The substrate in each of theaforementioned technologies should be uniform and solid with anon-porous surface (Schena (1999), supra). Suggested substrates includesilicon, silica, glass slides, glass chips, and silicon wafers.Alternatively, a procedure analogous to a dot or slot blot may also beused to arrange and link elements to the surface of a substrate usingthermal, UV, chemical, or mechanical bonding procedures. A typical arraymay be produced using available methods and machines well known to thoseof ordinary skill in the art and may contain any appropriate number ofelements. (See, e.g., Schena, M. et al. (1995) Science 270:467-470;Shalon, D. et al. (1996) Genome Res. 6:639-645; Marshall, A. and J.Hodgson (1998) Nat. Biotechnol. 16:27-31.)

[0321] Full length cDNAs, Expressed Sequence Tags (ESTs), or fragmentsor oligomers thereof may comprise the elements of the microarray.Fragments or oligomers suitable for hybridization can be selected usingsoftware well known in the art such as LASERGENE software (DNASTAR). Thearray elements are hybridized with polynucleotides in a biologicalsample. The polynucleotides in the biological sample are conjugated to afluorescent label or other molecular tag for ease of detection. Afterhybridization, nonhybridized nucleotides from the biological sample areremoved, and a fluorescence scanner is used to detect hybridization ateach array element. Alternatively, laser desorbtion and massspectrometry may be used for detection of hybridization. The degree ofcomplementarity and the relative abundance of each polynucleotide whichhybridizes to an element on the microarray may be assessed. In oneembodiment, microarray preparation and usage is described in detailbelow.

[0322] Tissue or Cell Sample Preparation

[0323] Total RNA is isolated from tissue samples using the guanidiniumthiocyanate method and poly(A)⁺RNA is purified using the oligo-(dT)cellulose method. Each poly(A)⁺ RNA sample is reverse transcribed usingMMLV reverse-transcriptase, 0.05 μg/μl oligo-(dT) primer (21mer),1×first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500μM dGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5(Amersham Pharmacia Biotech). The reverse transcription reaction isperformed in a 25 ml volume containing 200 ng poly(A)⁺ RNA withGEMBRIGHT kits (Incyte). Specific control poly(A)⁺ RNAs are synthesizedby in vitro transcription from non-coding yeast genomic DNA. Afterincubation at 37° C. for 2 hr, each reaction sample (one with Cy3 andanother with Cy5 labeling) is treated with 2.5 ml of 0.5M sodiumhydroxide and incubated for 20 minutes at 85° C. to the stop thereaction and degrade the RNA. Samples are purified using two successiveCHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc.(CLONTECH), Palo Alto Calif.) and after combining, both reaction samplesare ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodiumacetate, and 300 ml of 100% ethanol. The sample is then dried tocompletion using a SpeedVAC (Savant Instruments Inc., Holbrook N.Y.) andresuspended in 14 μl 5×SSC/0.2% SDS.

[0324] Microarray Preparation

[0325] Sequences of the present invention are used to generate arrayelements. Each array element is amplified from bacterial cellscontaining vectors with cloned cDNA inserts. PCR amplification usesprimers complementary to the vector sequences flanking the cDNA insert.Array elements are amplified in thirty cycles of PCR from an initialquantity of 1-2 ng to a final quantity greater than 5 μg. Amplifiedarray elements are then purified using SEPHACRYL-400 (Amersham PharmaciaBiotech).

[0326] Purified array elements are immobilized on polymer-coated glassslides. Glass microscope slides (Corning) are cleaned by ultrasound in0.1% SDS and acetone, with extensive distilled water washes between andafter treatments. Glass slides are etched in 4% hydrofluoric acid (VWRScientific Products Corporation (VWR), West Chester Pa.), washedextensively in distilled water, and coated with 0.05% aminopropyl silane(Sigma) in 95% ethanol. Coated slides are cured in a 110° C. oven.

[0327] Array elements are applied to the coated glass substrate using aprocedure described in U.S. Pat. No. 5,807,522, incorporated herein byreference. 1 μl of the array element DNA, at an average concentration of100 ng/μl, is loaded into the open capillary printing element by ahigh-speed robotic apparatus. The apparatus then deposits about 5 nl ofarray element sample per slide.

[0328] Microarrays are UV-crosslinked using a STRATALINKERUV-crosslinker (Stratagene). Microarrays are washed at room temperatureonce in 0.2% SDS and three times in distilled water. Non-specificbinding sites are blocked by incubation of microarrays in 0.2% casein inphosphate buffered saline (PBS) (Tropix, Inc., Bedford Mass.) for 30minutes at 60° C. followed by washes in 0.2% SDS and distilled water asbefore.

[0329] Hybridization

[0330] Hybridization reactions contain 9 μl of sample mixture consistingof 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5×SSC,0.2% SDS hybridization buffer. The sample mixture is heated to 65° C.for 5 minutes and is aliquoted onto the microarray surface and coveredwith an 1.8 cm² coverslip. The arrays are transferred to a waterproofchamber having a cavity just slightly larger than a microscope slide.The chamber is kept at 100% humidity internally by the addition of 140μl of 5×SSC in a corner of the chamber. The chamber containing thearrays is incubated for about 6.5 hours at 60° C. The arrays are washedfor 10 min at 45° C. in a first wash buffer (1×SSC; 0.1% SDS), threetimes for 10 minutes each at 45° C. in a second wash buffer (0.1×SSC),and dried.

[0331] Detection

[0332] Reporter-labeled hybridization complexes are detected with amicroscope equipped with an Innova 70 mixed gas 10 W laser (Coherent,Inc., Santa Clara Calif.) capable of generating spectral lines at 488 nmfor excitation of Cy3 and at 632 nm for excitation of Cy5. Theexcitation laser light is focused on the array using a 20×microscopeobjective (Nikon, Inc., Melville N.Y.). The slide containing the arrayis placed on a computer-controlled X-Y stage on the microscope andraster-scanned past the objective. The 1.8 cm×1.8 cm array used in thepresent example is scanned with a resolution of 20 micrometers.

[0333] In two separate scans, a mixed gas multiline laser excites thetwo fluorophores sequentially. Emitted light is split, based onwavelength, into two photomultiplier tube detectors (PMT R1477,Hamamatsu Photonics Systems, Bridgewater N.J.) corresponding to the twofluorophores. Appropriate filters positioned between the array and thephotomultiplier tubes are used to filter the signals. The emissionmaxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5.Each array is typically scanned twice, one scan per fluorophore usingthe appropriate filters at the laser source, although the apparatus iscapable of recording the spectra from both fluorophores simultaneously.

[0334] The sensitivity of the scans is typically calibrated using thesignal intensity generated by a cDNA control species added to the samplemixture at a known concentration. A specific location on the arraycontains a complementary DNA sequence, allowing the intensity of thesignal at that location to be correlated with a weight ratio ofhybridizing species of 1:100,000. When two samples from differentsources (e.g., representing test and control cells), each labeled with adifferent fluorophore, are hybridized to a single array for the purposeof identifying genes that are differentially expressed, the calibrationis done by labeling samples of the calibrating cDNA with the twofluorophores and adding identical amounts of each to the hybridizationmixture.

[0335] The output of the photomultiplier tube is digitized using a12-bit Rn-835H analog-to-digital (A/D) conversion board (Analog Devices,Inc., Norwood Mass.) installed in an IBM-compatible PC computer. Thedigitized data are displayed as an image where the signal intensity ismapped using a linear 20-color transformation to a pseudocolor scaleranging from blue (low signal) to red (high signal). The data is alsoanalyzed quantitatively. Where two different fluorophores are excitedand measured simultaneously, the data are first corrected for opticalcrosstalk (due to overlapping emission spectra) between the fluorophoresusing each fluorophore's emission spectrum.

[0336] A grid is superimposed over the fluorescence signal image suchthat the signal from each spot is centered in each element of the grid.The fluorescence signal within each element is then integrated to obtaina numerical value corresponding to the average intensity of the signal.The software used for signal analysis is the GEMTOOLS gene expressionanalysis program (kncyte).

[0337] XII. Complementary Polynucleotides

[0338] Sequences complementary to the GCREC-encoding sequences, or anyparts thereof, are used to detect, decrease, or inhibit expression ofnaturally occurring GCREC. Although use of oligonucleotides comprisingfrom about 15 to 30 base pairs is described, essentially the sameprocedure is used with smaller or with larger sequence fragments.Appropriate oligonucleotides are designed using OLIGO 4.06 software(National Biosciences) and the coding sequence of GCREC. To inhibittranscription, a complementary oligonucleotide is designed from the mostunique 5′ sequence and used to prevent promoter binding to the codingsequence. To inhibit translation, a complementary oligonucleotide isdesigned to prevent ribosomal binding to the GCREC-encoding transcript.

[0339] XIII. Expression of GCREC

[0340] Expression and purification of GCREC is achieved using bacterialor virus-based expression systems. For expression of GCREC in bacteria,cDNA is subcloned into an appropriate vector containing an antibioticresistance gene and an inducible promoter that directs high levels ofcDNA transcription. Examples of such promoters include, but are notlimited to, the trp-lac (tac) hybrid promoter and the T5 or T7bacteriophage promoter in conjunction with the lac operator regulatoryelement. Recombinant vectors are transformed into suitable bacterialhosts, e.g., BL21(DE3). Antibiotic resistant bacteria express GCREC uponinduction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expressionof GCREC in eukaryotic cells is achieved by infecting insect ormammalian cell lines with recombinant Autographica californica nuclearpolyhedrosis virus (AcMNPV), commonly known as baculovirus. Thenonessential polyhedrin gene of baculovirus is replaced with cDNAencoding GCREC by either homologous recombination or bacterial-mediatedtransposition involving transfer plasmid intermediates. Viralinfectivity is maintained and the strong polyhedrin promoter drives highlevels of cDNA transcription. Recombinant baculovirus is used to infectSpodoptera fruiperda (Sf9) insect cells in most cases, or humanhepatocytes, in some cases. Infection of the latter requires additionalgenetic modifications to baculovirus. (See Engelhard, E. K. et al.(1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996)Hum. Gene Ther. 7:1937-1945.)

[0341] In most expression systems, GCREC is synthesized as a fusionprotein with, e.g., glutathione S-transferase (GST) or a peptide epitopetag, such as FLAG or 6-His, permitting rapid, single-step,affinity-based purification of recombinant fusion protein from crudecell lysates. GST, a 26-kilodalton enzyme from Schistosoma laponicum,enables the purification of fusion proteins on immobilized glutathioneunder conditions that maintain protein activity and antigenicity(Amersham Pharmacia Biotech). Following purification, the GST moiety canbe proteolytically cleaved from GCREC at specifically engineered sites.FLAG, an 8-amino acid peptide, enables immunoaffinity purification usingcommercially available monoclonal and polyclonal anti-FLAG antibodies(Eastman Kodak). 6-His, a stretch of six consecutive histidine residues,enables purification on metal-chelate resins (QIAGEN). Methods forprotein expression and purification are discussed in Ausubel (1995,supra, ch. 10 and 16). Purified GCREC obtained by these methods can beused directly in the assays shown in Examples XVII, XVIII, and X=, whereapplicable.

[0342] XIV. Functional Assays

[0343] GCREC function is assessed by expressing the sequences encodingGCREC at physiologically elevated levels in mammalian cell culturesystems. cDNA is subcloned into a mammalian expression vector containinga strong promoter that drives high levels of cDNA expression. Vectors ofchoice include PCMV SPORT (Life Technologies) and PCR3.1 (Invitrogen,Carlsbad Calif.), both of which contain the cytomegalovirus promoter.5-10 μg of recombinant vector are transiently transfected into a humancell line, for example, an endothelial or hematopoietic cell line, usingeither liposome formulations or electroporation. 1-2 μg of an additionalplasmid containing sequences encoding a marker protein areco-transfected. Expression of a marker protein provides a means todistinguish transfected cells from nontransfected cells and is areliable predictor of cDNA expression from the recombinant vector.Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP;Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), anautomated, laser optics-based technique, is used to identify transfectedcells expressing GFP or CD64-GFP and to evaluate the apoptotic state ofthe cells and other cellular properties. FCM detects and quantifies theuptake of fluorescent molecules that diagnose events preceding orcoincident with cell death. These events include changes in nuclear DNAcontent as measured by staining of DNA with propidium iodide; changes incell size and granularity as measured by forward light scatter and 90degree side light scatter; down-regulation of DNA synthesis as measuredby decrease in bromodeoxyuridine uptake; alterations in expression ofcell surface and intracellular proteins as measured by reactivity withspecific antibodies; and alterations in plasma membrane composition asmeasured by the binding of fluorescein-conjugated Annexin V protein tothe cell surface. Methods in flow cytometry are discussed in Ormerod, M.G. (1994) Flow Cytometry, Oxford, New York N.Y.

[0344] The influence of GCREC on gene expression can be assessed usinghighly purified populations of cells transfected with sequences encodingGCREC and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed onthe surface of transfected cells and bind to conserved regions of humanimmunoglobulin G (IgG). Transfected cells are efficiently separated fromnontransfected cells using magnetic beads coated with either human IgGor antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can bepurified from the cells using methods well known by those of skill inthe art. Expression of mRNA encoding GCREC and other genes of interestcan be analyzed by northern analysis or microarray techniques.

[0345] XV. Production of GCREC Specific Antibodies

[0346] GCREC substantially purified using polyacrylamide gelelectrophoresis (PAGE; see, e.g., Harrington, M. G. (1990) MethodsEnzymol. 182:488-495), or other purification techniques, is used toimmunize animals (e.g., rabbits, mice, etc.) and to produce antibodiesusing standard protocols.

[0347] Alternatively, the GCREC amino acid sequence is analyzed usingLASERGENE software (DNASTAR) to determine regions of highimmunogenicity, and a corresponding oligopeptide is synthesized and usedto raise antibodies by means known to those of skill in the art. Methodsfor selection of appropriate epitopes, such as those near the C-terminusor in hydrophilic regions are well described in the art. (See, e.g.,Ausubel, 1995, supra, ch. 11.)

[0348] Typically, oligopeptides of about 15 residues in length aresynthesized using an ABI 431A peptide synthesizer (Applied Biosystems)using FMOC chemistry and coupled to Kiji (Sigma-Aldrich, St. Louis Mo.)by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) toincrease immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits areimmunized with the oligopeptide-KLH complex in complete Freund'sadjuvant. Resulting antisera are tested for antipeptide and anti-GCRECactivity by, for example, binding the peptide or GCREC to a substrate,blocking with 1% BSA, reacting with rabbit antisera, washing, andreacting with radio-iodinated goat anti-rabbit IgG.

[0349] XVI. Purification of Naturally Occurring GCREC Using SpecificAntibodies

[0350] Naturally occurring or recombinant GCREC is substantiallypurified by immunoaffinity chromatography using antibodies specific forGCREC. An immunoaffinity column is constructed by covalently couplinganti-GCREC antibody to an activated chromatographic resin, such asCNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After thecoupling, the resin is blocked and washed according to themanufacturer's instructions.

[0351] Media containing GCREC are passed over the immunoaffinity column,and the column is washed under conditions that allow the preferentialabsorbance of GCREC (e.g., high ionic strength buffers in the presenceof detergent). The column is eluted under conditions that disruptantibody/GCREC binding (e.g., a buffer of pH 2 to pH 3, or a highconcentration of a chaotrope, such as urea or thiocyanate ion), andGCREC is collected.

[0352] XVII. Identification of Molecules Which Interact with GCREC

[0353] Molecules which interact with GCREC may include agonists andantagonists, as well as molecules involved in signal transduction, suchas G proteins. GCREC, or a fragment thereof, is labeled with ¹²⁵IBolton-Hunter reagent. (See, e.g., Bolton A. E. and W. M. Hunter (1973)Biochem. J. 133:529-539.) A fragment of GCREC includes, for example, afragment comprising one or more of the three extracellular loops, theextracellular N-terminal region, or the third intracellular loop.Candidate molecules previously arrayed in the wells of a multi-wellplate are incubated with the labeled GCREC, washed, and any wells withlabeled GCREC complex are assayed. Data obtained using differentconcentrations of GCREC are used to calculate values for the number,affinity, and association of GCREC with the candidate ligand molecules.

[0354] Alternatively, molecules interacting with GCREC are analyzedusing the yeast two-hybrid system as described in Fields, S. and O. Song(1989) Nature 340:245-246, or using commercially available kits based onthe two-hybrid system, such as the MATCHMAKER system (Clontech). GCRECmay also be used in the PATHCALLING process (CuraGen Corp., New HavenConn.) which employs the yeast two-hybrid system in a high-throughputmanner to determine all interactions between the proteins encoded by twolarge libraries of genes (Nandabalan, K. et al. (2000) U.S. Pat. No.6,057,101).

[0355] Potential GCREC agonists or antagonists may be tested foractivation or inhibition of GCREC receptor activity using the assaysdescribed in sections XVII and XVEII. Candidate molecules may beselected from known GPCR agonists or antagonists, peptide libraries, orcombinatorial chemical libraries.

[0356] Methods for detecting interactions of GCREC with intracellularsignal transduction molecules such as G proteins are based on thepremise that internal segments or cytoplasmic domains from an orphan Gprotein-coupled seven transmembrane receptor may be exchanged with theanalogous domains of a known G protein-coupled seven transmembranereceptor and used to identify the G-proteins and downstream signalingpathways activated by the orphan receptor domains (Kobilka, B. K. et al.(1988) Science 240:1310-1316). In an analogous fashion, domains of theorphan receptor may be cloned as a portion of a fusion protein and usedin binding assays to demonstrate interactions with specific G proteins.Studies have shown that the third intracellular loop of Gprotein-coupled seven transmembrane receptors is important for G proteininteraction and signal transduction (Conklin, B. R. et al. (1993) Cell73:631-641). For example, the DNA fragment corresponding to the thirdintracellular loop of GCREC may be amplified by the polymerase chainreaction (PCR) and subcloned into a fusion vector such as pGEX(Pharmacia Biotech). The construct is transformed into an appropriatebacterial host, induced, and the fusion protein is purified from thecell lysate by glutathione-Sepharose 4B (Pharmacia Biotech) affinitychromatography.

[0357] For in vitro binding assays, cell extracts containing G proteinsare prepared by extraction with 50 mM Tris, pH 7.8, 1 mM EGTA, 5 mMMgCl₂, 20 mM CHAPS, 20% glycerol, 10 μg of both aprotinin and leupeptin,and 20 μl of 50 mM phenylmethylsulfonyl fluoride. The lysate isincubated on ice for 45 min with constant stirring, centrifuged at23,000 g for 15 min at 4° C., and the supernatant is collected. 750 μgof cell extract is incubated with glutathione S-transferase (GST) fusionprotein beads for 2 h at 4° C. The GST beads are washed five times withphosphate-buffered saline. Bound G subunits are detected by[³²P]ADP-ribosylation with pertussis or cholera toxins. The reactionsare terminated by the addition of SDS sample buffer (4.6% (w/v) SDS, 10%(v/v) β-mercaptoethanol, 20% (w/v) glycerol, 95.2 mM Tris-HCl, pH 6.8,0.01% (w/v) bromphenol blue). The [³²P]ADP-labeled proteins areseparated on 10% SDS-PAGE gels, and autoradiographed. The separatedproteins in these gels are transferred to nitrocellulose paper, blockedwith blotto (5% nonfat dried milk, 50 mM Tris-HCl (pH 8.0), 2 mM CaCl,80 mM NaCl, 0.02% NaN₃, and 0.2% Nonidet P-40) for 1 hour at roomtemperature, followed by incubation for 1.5 hours with Gα subtypeselective antibodies (1:500; Calbiochem-Novabiochem). After threewashes, blots are incubated with horseradish peroxidase (HRP)-conjugatedgoat anti-rabbit immunoglobulin (1:2000, Cappel, Westchester Pa.) andvisualized by the chemiluminescence-based ECL method (Amersham Corp.).

[0358] XVIII. Demonstration of GCREC Activity

[0359] An assay for GCREC activity measures the expression of GCREC onthe cell surface. cDNA encoding GCREC is transfected into an appropriatemammalian cell line. Cell surface proteins are labeled with biotin asdescribed (de la Fuente, M. A. et al. (1997) Blood 90:2398-2405).Immunoprecipitations are performed using GCREC-specific antibodies, andimmunoprecipitated samples are analyzed using sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE) and immunoblottingtechniques. The ratio of labeled immunoprecipitant to unlabeledimmunoprecipitant is proportional to the amount of GCREC expressed onthe cell surface.

[0360] In the alternative, an assay for GCREC activity is based on aprototypical assay for ligand/receptor-mediated modulation of cellproliferation. This assay measures the rate of DNA synthesis in Swissmouse 3T3 cells. A plasmid containing polynucleotides encoding GCREC isadded to quiescent 3T3 cultured cells using transfection methods wellknown in the art. The transiently transfected cells are then incubatedin the presence of [³H]thymidine, a radioactive DNA precursor molecule.Varying amounts of GCREC ligand are then added to the cultured cells.Incorporation of [³H]thymidine into acid-precipitable DNA is measuredover an appropriate time interval using a radioisotope counter, and theamount incorporated is directly proportional to the amount of newlysynthesized DNA. A linear dose-response curve over at least ahundred-fold GCREC ligand concentration range is indicative of receptoractivity. One unit of activity per milliliter is defined as theconcentration of GCREC producing a 50% response level, where 100%represents maximal incorporation of [³H]thymidine into acid-precipitableDNA (McKay, I. and I. Leigh, eds. (1993) Growth Factors: A PracticalApproach, Oxford University Press, New York N.Y., p. 73.)

[0361] In a further alternative, the assay for GCREC activity is basedupon the ability of GPCR family proteins to modulate G protein-activatedsecond messenger signal transduction pathways (e.g., cAMP; Gaudin, P. etal. (1998) J. Biol. Chem. 273:4990-4996). A plasmid encoding full lengthGCREC is transfected into a mammalian cell line (e.g., Chinese hamsterovary (CHO) or human embryonic kidney (HEK-293) cell lines) usingmethods well-known in the art. Transfected cells are grown in 12-welltrays in culture medium for 48 hours, then the culture medium isdiscarded, and the attached cells are gently washed with PBS. The cellsare then incubated in culture medium with or without ligand for 30minutes, then the medium is removed and cells lysed by treatment with 1M perchloric acid. The cAMP levels in the lysate are measured byradioimmunoassay using methods well-known in the art. Changes in thelevels of cAMP in the lysate from cells exposed to ligand compared tothose without ligand are proportional to the amount of GCREC present inthe transfected cells.

[0362] To measure changes in inositol phosphate levels, the cells aregrown in 24-well plates containing 1×10⁵ cells/well and incubated withinositol-free media and [³H]myoinositol, 2 μCi/well, for 48 hr. Theculture medium is removed, and the cells washed with buffer containing10 mM LiCl followed by addition of ligand. The reaction is stopped byaddition of perchloric acid. Inositol phosphates are extracted andseparated on Dowex AG1-X8 (Bio-Rad) anion exchange resin, and the totallabeled inositol phosphates counted by liquid scintillation. Changes inthe levels of labeled inositol phosphate from cells exposed to ligandcompared to those without ligand are proportional to the amount of GCRECpresent in the transfected cells.

[0363] XIX. Identification of GCREC Ligands

[0364] GCREC is expressed in a eukaryotic cell line such as CHO (ChineseHamster Ovary) or HEK (Human Embryonic Kidney) 293 which have a goodhistory of GPCR expression and which contain a wide range of G-proteinsallowing for functional coupling of the expressed GCREC to downstreameffectors. The transformed cells are assayed for activation of theexpressed receptors in the presence of candidate ligands. Activity ismeasured by changes in intracellular second messengers, such as cyclicAMP or Ca²⁺. These may be measured directly using standard methods wellknown in the art, or by the use of reporter gene assays in which aluminescent protein (e.g. firefly luciferase or green fluorescentprotein) is under the transcriptional control of a promoter responsiveto the stimulation of protein kinase C by the activated receptor(Milligan, G. et al. (1996) Trends Pharmacol. Sci. 17:235-237). Assaytechnologies are available for both of these second messenger systems toallow high throughput readout in multi-well plate format, such as theadenylyl cyclase activation FlashPlate Assay (NEN Life SciencesProducts), or fluorescent Ca²⁺ indicators such as Fluo-4 AM (MolecularProbes) in combination with the FLIPR fluorimetric plate reading system(Molecular Devices). In cases where the physiologically relevant secondmessenger pathway is not known, GCREC may be coexpressed with theG-proteins G_(α15/16) which have been demonstrated to couple to a widerange of G-proteins (Offermanns, S. and M. I. Simon (1995) J. Biol.Chem. 270:15175-15180), in order to funnel the signal transduction ofthe GCREC through a pathway involving phospholipase C and Ca²⁺mobilization. Alternatively, GCREC may be expressed in engineered yeastsystems which lack endogenous GPCRs, thus providing the advantage of anull background for GCREC activation screening. These yeast systemssubstitute a human GPCR and G_(α). protein for the correspondingcomponents of the endogenous yeast pheromone receptor pathway.Downstream signaling pathways are also modified so that the normal yeastresponse to the signal is converted to positive growth on selectivemedia or to reporter gene expression (Broach, J. R. and J. Thorner(1996) Nature 384 (supp.):14-16). The receptors are screened againstputative ligands including known GPCR ligands and other naturallyoccurring bioactive molecules. Biological extracts from tissues,biological fluids and cell supernatants are also screened.

[0365] Various modifications and variations of the described methods andsystems of the invention will be apparent to those skilled in the artwithout departing from the scope and spirit of the invention. Althoughthe invention has been described in connection with certain embodiments,it should be understood that the invention as claimed should not beunduly limited to such specific embodiments. Indeed, variousmodifications of the described modes for carrying out the inventionwhich are obvious to those skilled in molecular biology or relatedfields are intended to be within the scope of the following claims.TABLE 1 Incyte Incyte Polypeptide Incyte Polynucleotide PolynucleotideProject ID SEQ ID NO: Polypeptide ID SEQ ID NO: ID CA2 Reagents 74752221 7475222CD1 74 7475222CB1 7476060 2 7476060CD1 75 7476060CB1 7476084 37476084GD1 76 7476084CB1 90080203CA2 7476110 4 7476110CD1 77 7476110CB17476774 5 7476774GD1 78 7476774CB1 90100709CA2 7477364 6 7477364GD1 797477364CB1 90100161CA2, 90100177CA2, 90100185CA2, 90100193CA2,90100285CA2 7477694 7 7477694CD1 80 7477694CB1 90100322CA2, 90100346CA2,90100422CA2 7477940 8 7477940GD1 81 7477940CB1 90055816CA2 7477944 97477944CD1 82 7477944CB1 90079736CA2, 90079804CA2 7480405 10 7480405GD183 7480405CB1 90057762CA2 7482486 11 7482486CD1 84 7482486CB1 7482535 127482535GD1 85 7482535CB1 90157475CA2, 90157559CA2 7482770 13 7482770GD186 7482770CB1 90100107CA2, 90100131CA2, 90100215CA2, 9010023ICA2,90100239CA2, 90100247CA2, 90100307CA2, 90100315CA2, 90100339CA2,90100415CA2 7475695 14 7475695CD1 87 7475695CB1 90106742CA2 7477365 157477365GD1 88 7477365CB1 90100353CA2, 90100369CA2, 90100377CA2,90100393CA2, 90100477CA2, 90100485CA2, 90100493CA2 7479899 16 7479899GD189 7479899CB1 90100817CA2, 90100825CA2, 90100841CA2 7480412 177480412GD1 90 7480412CB1 9010066ICA2, 90100737CA2 7485460 18 7485460CD191 7485460CB1 90100464CA2, 90100472CA2, 90100541CA2, 90100625CA2,90100641CA2 7472173 19 7472173CD1 92 7472173CB1 90100829CA2, 90100845CA27475690 20 7475690CD1 93 7475690CB1 7476068 21 7476068CD1 94 7476068CB190100704CA2 7476i63 22 7476163CD1 95 7476163CB1 90100252CA2,90100268CA2, 90100284CA2 7476166 23 7476166CD1 96 7476166CB1 90127623CA27476686 24 7476686CD1 97 7476686CB1 90079904CA2 7477363 25 7477363CD1 987477363CB1 90100348CA2, 90100432CA2 7477368 26 7477368CD1 99 7477368CB190100164CA2, 90100172CA2, 90100180CA2, 90100188CA2 7480408 27 7480408CD1100 7480408CB1 90100702CA2, 90100802CA2, 90100818CA2, 90100834CA27480409 28 7480409CD1 101 7480409CB1 90100766CA2, 90100882CA290100890CA2 7482487 29 7482487CD1 102 7482487CB1 90056164CA2,90056172CA2, 90056180CA2, 90056188CA2, 90056196CA2, 90056256CA2,90056280CA2 7485424 30 7485424CD1 103 7485424CB1 90108580CA2 7475196 317475196CD1 104 7475196CB1 90149657CA2, 90149665CA2, 9014968ICA2,90149689CA2, 90149749CA2, 90149765CA2, 90149773CA2 7475295 32 7475295CD1105 7475295CB1 90079750CA2, 90079766CA2, 90079866CA2 7478361 337478361CD1 106 7478361CB1 90080273CA2 7482534 34 7482534CD1 1077482534CB1 9010085ICA2 7490493 35 7490493CD1 108 7490493CB1 90157612CA2,90157644CA2 58001274 36 58001274CD1 109 58001274CB1 7476809 377476809CD1 110 7476809CB1 7476048 38 7476048CD1 111 7476048CB1 747667939 7476679CD1 112 7476679CB1 7486996 40 7486996CD1 113 7486996CB17490489 41 7490489CD1 114 7490489CB1 7475304 42 7475304CD1 1157475304CB1 7475248 43 7475248CD1 116 7475248CB1 7475191 44 7475191CD1117 7475191CB1 7480413 45 7480413CD1 118 7480413CB1 7476165 467476165CD1 119 7476165CB1 7478345 47 7478345CD1 120 7478345CB1 747524548 7475245CD1 121 7475245CB1 7485481 49 7485481CD1 122 7485481CB17482835 50 7482835CD1 123 7482835CB1 7475100 51 7475100CD1 1247475100CB1 7475185 52 7475185CD1 125 7475185CB1 90168702CA2 7477369 537477369CD1 126 7477369CB1 7495138 54 7495138CD1 127 7495138CB1 747583055 7475830CD1 128 7475830CB1 90086852CA2, 90086860CA2, 90086892CA27476161 56 7476161CD1 129 7476161CB1 90086823CA2, 90086839CA2,7475235CD1 90086847CA2 7475235 57 7475235CD1 130 7475235CB1 90067365CA27476246 58 7476246CD1 131 7476246CB1 7474899 59 7474899CD1 1327474899CB1 90086506CA2, 90086522CA2, 90086530CA2, 90086538CA2,90086614CA2, 90086622CA2, 90086638CA2, 90086646CA2 90090093CA2 747835360 7478353CD1 133 7478353CB1 90079945CA2, 90079953CA2, 9007996ICA2,90079985CA2 90080077CA2, 90080085CA2, 90080206CA2, 90080393CA2 747391061 7473910CD1 134 7473910CB1 90079835CA2, 90079843CA2, 90079891CA27476047 62 7476047CD1 135 7476047CB1 90110172CA2 7289994 63 7289994GD1136 7289994CB1 7482840 64 7482840CD1 137 7482840CB1 90067365CA2 5509363165 55093631CD1 138 55093631CB1 7474992 66 7474992CD1 139 7474992CB17476244 67 7476244CD1 140 7476244CB1 90066956CA2, 90066964CA2,90066972CA2, 90066980CA2, 90066988CA2, 90067072CA2, 90067080CA2,90067088CA2 7487604 68 7487604CD1 141 7487604CB1 7483200 69 7483200CD1142 7483200CB1 7476069 70 7476069CD1 143 7476069CB1 90079578CA2,90079586CA2, 90079594CA2, 90079662CA2 90079670CA2, 90079678CA2,90079686CA2, 90079694CA2, 90079813CA2 7472453 71 7472453CD1 1447472453CB1 90079963CA2, 9007997ICA2, 90079979CA2, 90080071CA2,9008045ICA2 5492483 72 5492483CD1 145 5492483CB1 90067309CA2,90067417CA2 7472079 73 7472079CD1 146 7472079CB1 90066764CA2,90066780CA2, 90066796CA2

[0366] TABLE 2 Polypeptide GenBank ID NO: SEQ Incyte or PROTEOMEProbability ID NO: Polypeptide ID ID NO: Score Annotation 1 7475222CD1g10644519 1.0E−110 [Mus musculus] odorant receptor Branscomb, A. et al.(2000) Evolution of odorant receptors expressed in mammalian testes.Genetics 156 (2), 785-797 2 7476060CD1 g18480240 1.0E−143 olfactoryreceptor MOR136-14 [Mus musculus] Zhang, X. and Firestein, S. (2000) Theolfactory receptor gene superfamily of the mouse. Nat. Neurosci. 5 (2),124-133 3 7476084CD1 g14582607 3.0E−82 olfactory receptor sdolf [Homosapiens] 7476084CD1 g3983374 6.3E−70 [Mus musculus] olfactory receptorC6 Krautwurst, D. et al. (1998) Identification of ligands for olfactoryreceptors by functional expression of a receptor library. Cell 95 (7),917-926 4 7476110CD1 g7211221 1.7E−106 [Papio hamadryas] olfactoryreceptor Rouquier, S. et al. (2000) The olfactory receptor generepertoire in primates and mouse: evidence for reduction of thefunctional fraction in primates. Proc. Natl. Acad. Sci. U.S.A. 97 (6),2870-2874 5 7476774CD1 g4680254 3.7E−113 [Mus musculus] odorant receptorS1 Malnic, B. et al. (1999) Combinatorial receptor codes for odors. Cell96 (5), 713-723 6 7477364CD1 g18479952 1.0E−151 olfactory receptorMOR207-1 [Mus musculus] 7 7477694CD1 g18479806 1.0E−145 olfactoryreceptor MOR262-7 [Mus musculus] 8 7477940CD1 g6178006 1.2E−91 [Musmusculus] odorant receptor MOR83 Tsuboi A. et al. (1999) Olfactoryneurons expressing closely linked and homologous odorant receptor genestend to project their axons to neighboring glomeruli on the olfactorybulb. J. Neurosci. 19(19): 8409-8418 7477940CD1 g18480846 1.0E−118olfactory receptor MOR246-2 [Mus musculus] 9 7477944CD1 g184795181.0E−142 olfactory receptor MOR232-3 [Mus musculus] 10 7480405CD1g18480488 1.0E−138 olfactory receptor MOR275-2 [Mus musculus] 117482486CD1 g18480488 1.0E−119 olfactory receptor MOR275-2 [Mus musculus]11 7482486CD1 g3983382 5.0E−77 [Mus musculus] olfactory receptor E3Krautwurst, D. et al. (1998) Identification of ligands for olfactoryreceptors by functional expression of a receptor library. Cell 95 (7),917-926 12 7482535CD1 g1256391 5.2E−123 [Rattus norvegicus] taste budreceptor protein TB 567 Thomas, M. B. ET AL. (1996) Chemoreceptorsexpressed in taste, olfactory and male reproductive tissues. Gene 178(1-2), 1-5 13 7482770CD1 g7211245 1.0E−118 olfactory receptor [Hylobateslar] Rouquier, S. et al. (2000) The olfactory receptor gene repertoirein primates and mouse: evidence for reduction of the functional fractionin primates. Proc. Natl. Acad. Sci. U.S.A. 97 (6), 2870-2874 147475695CD1 g18479966 1.0E−107 olfactory receptor MOR103-10 [Musmusculus] 7475695CD1 g3983437 1.0E−102 olfactory receptor 17 [Musmusculus] Krautwurst, D. et al. (1998) Identification of ligands forolfactory receptors by functional expression of a receptor library. Cell95 (7), 917-926 15 7477365CD1 g18479796 1.0E−145 olfactory receptorMOR172-2 [Mus musculus] 16 7479899CD1 g18480446 1.0E−125 olfactoryreceptor MOR147-2 [Mus musculus] 17 7480412CD1 g18480488 1.0E−135olfactory receptor MOR275-2 [Mus musculus] 18 7485460CD1 g184800861.0E−148 olfactory receptor MOR202-5 [Mus musculus] 19 7472173CD1g18480262 1.0E−154 olfactory receptor MOR104-3 [Mus musculus] 207475690CD1 g18480350 1.0E−149 olfactory receptor MOR213-3 [Mus musculus]21 7476068CD1 g18479312 1.0E−155 olfactory receptor MOR31-4 [Musmusculus] 22 7476163CD1 g18479868 1.0E−143 olfactory receptor MOR239-1[Mus musculus] 23 7476166CD1 g18480126 1.0E−148 olfactory receptorMOR239-2 [Mus musculus] 24 7476686CD1 g18480508 1.0E−138 olfactoryreceptor MOR247-2 [Mus musculus] 25 7477363CD1 g18480306 1.0E−143olfactory receptor MOR181-2 [Mus musculus] 26 7477368CD1 g184807581.0E−121 olfactory receptor MOR246-5 [Mus musculus] 26 7477368CD1g6178006 4.5E−92 [Mus musculus] odorant receptor MOR83 Tsuboi A. et al.(1999) Olfactory neurons expressing closely linked and homologousodorant receptor genes tend to project their axons to neighboringglomeruli on the olfactory bulb. J. Neurosci. 19(19): 8409-8418 277480408CD1 g3983382 3.0E−95 [Mus musculus] olfactory receptor E3Krautwurst, D., et al. (1998) Identification of ligands for olfactoryreceptors by functional expression of a receptor library. Cell 95 (7),917-926 28 7480409CD1 g18480252 1.0E−106 olfactory receptor MOR220-2[Mus musculus] 29 7482487CD1 g3983382 2.1E−85 [Mus musculus] olfactoryreceptor E3 Krautwurst, D., et al. (1998) Identification of ligands forolfactory receptors by functional expression of a receptor library. Cell95 (7), 917-926 30 7485424CD1 g3983384 7.8E−104 [Mus musculus] olfactoryreceptor E6 Krautwurst, D. et al. (1998) Identification of ligands forolfactory receptors by functional expression of a receptor library. Cell95 (7), 917-926 31 7475196CD1 g18479240 1.0E−159 olfactory receptorMOR7-1 [Mus musculus] 32 7475295CD1 g15293637 1.0E−111 olfactoryreceptor [Homo sapiens] 33 7478361CD1 g18480558 1.0E−144 olfactoryreceptor MOR256-27 [Mus musculus] 34 7482534CD1 g18480824 1.0E−163olfactory receptor MOR224-9 [Mus musculus] 35 7490493CD1 g184808721.0E−145 olfactory receptor MOR268-5 [Mus musculus] 36 58001274CD1g18480770 1.0E−153 olfactory receptor MOR271-1 [Mus musculus] 377476809CD1 g18480872 1.0E−143 olfactory receptor MOR268-5 [Mus musculus]38 7476048CD1 g18480764 1.0E−149 olfactory receptor MOR14-9 [Musmusculus] 39 7476679CD1 g15986319 0.0E+00 human breast cancer amplifiedG-protein coupled receptor 3 (BCA-GPCR-3) [Homo sapiens] 40 7486996CD1g7211522 9.2E−80 [Gorilla gorilla] olfactory receptor 41 7490489CD1g18480894 1.0E−155 olfactory receptor MOR261-12 [Mus musculus] 427475304CD1 g18479450 1.0E−148 olfactory receptor MOR188-3 [Mus musculus]43 7475248CD1 g18480332 9.0E−97 olfactory receptor MOR201-2 [Musmusculus] 7475248CD1 g18480782 3.0E−96 olfactory receptor MOR176-2 [Musmusculus] 44 7475191CD1 g18480716 1.0E−154 olfactory receptor MOR120-2[Mus musculus] 45 7480413CD1 g15293809 1.0E−122 olfactory receptor [Homosapiens] 46 7476165CD1 g18480132 1.0E−161 olfactory receptor MOR239-5[Mus musculus] 47 7478345CD1 g18479612 1.0E−148 olfactory receptorMOR269-1 [Mus musculus] 48 7475245CD1 g18479786 1.0E−138 olfactoryreceptor MOR174-1 [Mus musculus] 49 7485481CD1 g18480334 1.0E−143olfactory receptor MOR199-1 [Mus musculus] 50 7482835CD1 g184808341.0E−143 olfactory receptor MOR25-1 [Mus musculus] 51 7475100CD1g18480596 1.0E−151 olfactory receptor MOR245-3 [Mus musculus] 527475185CD1 g18480010 1.0E−139 olfactory receptor MOR204-8 [Mus musculus]53 7477369CD1 g18480506 1.0E−155 olfactory receptor MOR247-1 [Musmusculus] 54 7495138CD1 g18479906 1.0E−127 olfactory receptor MOR231-11[Mus musculus] 55 7475830CD1 g18479448 1.0E−168 olfactory receptorMOR185-3 [Mus musculus] 56 7476161CD1 g18480354 1.0E−134 olfactoryreceptor MOR213-5 [Mus musculus] 57 7475235CD1 g18479242 1.0E−132olfactory receptor MOR8-1 [Mus musculus] 58 7476246CD1 g11967419 6.5E−79[Mus musculus] vomeronasal receptor VIRC3 Del Punta, K. et al. (2000)Sequence Diversity and Genomic Organization of Vomeronasal ReceptorGenes in the Mouse. Genome Res. 10: 1958-1967 59 7474899CD1 g184793861.0E−156 olfactory receptor MOR40-2 [Mus musculus] 60 7478353CD1g1246534 2.1E−89 [Gallus gallus] olfactory receptor 4 Leibovici, M., etal. (1996) Dev. Biol. 175, 118-131 7478353CD1 g18480124 1.0E−122olfactory receptor MOR215-3 [Mus musculus] 61 7473910CD1 g184802021.0E−139 olfactory receptor MOR174-8 [Mus musculus] 62 7476047CD1g18479296 2.0E−92 olfactory receptor MOR14-4 [Mus musculus] 637289994CD1 g3789765 7.4E−252 [Homo sapiens] transmembrane receptor UNC5CAckerman, S. L. and Knowles, B. B. (1998) Genomics 52, 205-208 647482840CD1 g18479242 1.0E−134 olfactory receptor MOR8-1 [Mus musculus]65 55093631CD1 g18479986 1.0E−162 olfactory receptor MOR31-12 [Musmusculus] 66 7474992CD1 g18480134 1.0E−160 olfactory receptor MOR210-1[Mus musculus] 67 7476244CD1 g18479686 1.0E−160 olfactory receptorMOR230-3 [Mus musculus] 68 7487604CD1 g18479836 1.0E−151 olfactoryreceptor MOR262-8 [Mus musculus] 69 7483200CD1 g18479792 1.0E−174olfactory receptor MOR188-5 [Mus musculus] 70 7476069CD1 g184792621.0E−107 olfactory receptor MOR16-1 [Mus musculus] 71 7472453CD1g18479770 1.0E−151 olfactory receptor MOR171-4 [Mus musculus] 725492483CD1 g18480490 1.0E−136 olfactory receptor MOR285-1 [Mus musculus]73 7472079CD1 g18479386 1.0E−140 olfactory receptor MOR40-2 [Musmusculus]

[0367] TABLE 3 SEQ Incyte Amino Potential ID Polypeptide AcidPhosphorylation Potential Methods Analytical NO: ID Residues SitesGlycosylation Sites Signature Sequences, Domains and Motifs andDatabases 1 7475222CD1 309 S65 S301 T190 N6 N225 7 transmembranereceptor (rhodopsin family): G39- HMMER_PFAM T262 T286 Y58 Y285TRANSMEMBRANE DOMAINS: A20-S48, E93- TMAP Y121, Q137-P165, F191-I219,A234-F254, T264- I284 N terminus is cytosolic. G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS T277-K293, K88-P127, E229-L255Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:V24-548. M57-K78, F102-I124, K233- F254, V197-L220, A234-R258, K267-K293Olfactory receptor signature PR00245: M57-K78, BLIMPS_PRINTS Y175-D189,L235-G250, V269-L280, T286-W300 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN: MULTIGENE FAMILYPD000921: L164-1242 OLFACTORY REGEPTOR PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: T243-K303G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|S29710|15-301: L15-W300DM00013|P23266|17-306: L15-L299 DM00013|P37067|17-306: L15-L299DM00013|S51356|18-307: L15-R298 2 7476060CD1 322 S8 S188 N5 N316 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM S230 S291Y290 TRANSMEMBRANE DOMAINS: Q23-L51, P58- TMAP M83, V92-S 117, S 139-S167, N195-V223 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: I207- BLIMPS_BLOCKS Y218, S188-1214, T282-K298,L90-P129 G-protein coupled receptors signature: Y102-G147 PROFILESCANOlfactory receptor signature PR00245: M59-K80, BLIMPS_PRINTS Y177-D191,L238-R253, A274-L285, S291-L305 RECEPTOR OLFACTORY GPROTEIN COUPLEDBLAST_PRODOM TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921:L166-L245 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: S246-R307OLFACTORY PROTEIN 19 GPROTEIN COUPLED BLAST_PRODOM RECEPTORTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY OLFACTION PD048705: M1-H54G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P30955|18-305: P18-L305DM00013|P23274|18-306: P18-L305 DM00013|S29707|18-306: P18-L301DM00013|P23272|18-306: P18-L305 G-protein coupled receptors signature:L110-I126 MOTIFS 3 7476084CD1 313 S17 S65 S186 T294 N3 N63 N292 7transmembrane receptor (rhodopsin family): G39- HMMER_PFAM L288TRANSMEMBRANE DOMAINS: A23-T51, P56- TMAP S81, Q98-A123, L133-R161,R191-1219, S231-R259, K270-L288 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: K88- BLIMPS_BLOCKS P127,A263-T289,T280-K296 G-protein coupled receptors signature: Y100-A145 PROFILESCANOlfactory receptor signature PR00245: M57-R78, BLIMPS_PRINTS F175-D189,F236-S251, V272-L283 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-L243G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23267|20-309: F29-Q300DM00013|P23270|18-311: F15-Q300 DM00013|P23272|18-306: E20-Q300DM00013|S29707|18-306: E20-Q300 Leucine zipper pattern: L185-L206L192-L213 MOTIFS G-protein coupled receptors signature: T108-I124 MOTIFS4 7476110CD1 313 S18 S67 S137 S188 N5 N65 7 transmembrane receptor(rhodopsin family): G41- HMMER_PFAM S291 T268 T310 Y290 TRANSMEMBRANEDOMAINS: C33-S53, P58- TMAP 178, Q100-F123, L138-R165, V194-I221,S239-Y259 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: K90- BLIMPS_BLOCKS P129, I207-Y218, S188-I214.T282-K298 G-protein coupled receptors signature: Y102-L148 PROFILESCANRhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:L26-550, M59-K80, F104-1126, L140- L161, I199-L222, K272-K298 Olfactoryreceptor signature PR00245: M59-K80, BLIMPS_PRINTS Y177-D191, F238-G253,S274-L285, S291-V305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLASTPRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: S246-S311 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|P30955|18-305: P21-V305DM00013|P23266|17-306: L17-V305 DM00013|P30953|18-306: K20-N306DM00013|P23274|18-306: E22-V305 G-protein coupled receptors signatureV110-I126 MOTIFS 5 7476774CD1 330 S309 T155 N21 Signal Peptide: M41-G61,M41-A62, M41-V67, HMMER M41-K68 7 transmembrane receptor (rhodopsinfamily): G59- HMMER_PFAM Y308 TRANSMEMBRANE DOMAINS: R39-A66, L81- TMAPV101, C115-V135, GI56-L184, C217-C245, A250- Y277 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: K108-BLIMPS_BLOCKS P147, I225-Y236, T253-S279, T300-K316 G-protein coupledreceptors signature: Y120-V165 PROFILESCAN Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: M77-N98, F122-I144,F158-V179, C217- I240, I160-L184, K290-K316, C44-K68 Olfactory receptorsignature PR00245: M77-N98, BLIMPS_PRINTS L195-S209, F256-G271,I292-L303, S309-L323 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L184-M264OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V265-G324 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|P23274|18-306: E40-L323DM00013|P30955|18-305: E40-L323 DM00013|P23266|17-306: Q38-L323DM00013|P23272|18-306: E40-L323 G-protein coupled receptors signature:T128.I144 MOTIFS 6 7477364CD1 310 S87 S137 S187 N5 N263 7 transmembranereceptor (rhodopsin family): G41- HMMER_PFAM S290 T78 Y289 TRANSMEMBRANEDOMAINS: L23-L43, M51- TMAP I71, S91-S117, L144-S172, V197-L225,F237-Y258, T268-I288 N terminus is non-cytosolic. G-protein coupledreceptors proteins BL00237: R90- BLIMPS_BLOCKS P129, Q234-Q260,I281-K297 G-protein coupled receptors signature: Y102-M147 PROFILE_SCANOlfactory receptor signature PR00245: M59-K80, BLIMPS_PRINTS F176-D190,F237-G252, A273-L284, S290-I304 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD000921: L166-M245 OLFACTORY RECEPTOR PROTEIN OPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: V247-K307OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD002495: N5-S53 G-PRQTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S51356|18-307: P21-R302DM00013|S29709|11-299: N19-1304 DM00013|P37067|17-306: N19-V303DM00013|P30955|18-305: P21-1304 G-protein coupled receptors signature:C110-I126 MOTIFS 7 7477694CD1 320 S67 S93 S270 S297 N5 N65 N315 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM T8 Y296TRANSMEMBRANE DOMAINS: L23-F51, Y73- TMAP K91, 593-TI 17. F177-1197,1205-1225. E232-Y259, E273-N292 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: L207- BLIMPS_BLOCKS Y2 18.E232-M258, T288-K304, K90-P 129 G-protein coupled receptors signature:F102-A146 PROFILESCAN Visual pigments (opsins) retinal binding site:A266- PROFILESCAN K321 Rhodopsin-like GPCR superfamily signatureBLIMPS_PRINTS PR00237: V26-150, M59-L80, 5 104-1126, G201- V222,M199-V222, A237-K261. A278-K304 Olfactory receptor signature PR00245:M59-L80, BLIMPS_PRINTS F177-D191. F238-G253, 1280-L291, 5297-L311RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245 OLFACTORY RECEPTORPROTEIN OPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD149621: T246-K314 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P23275|17-306: L17-L311 DM00013|A57069|15-304:518-L311 DM00013|P23274|18-306: Q24-C312 DM00013|S29707|18-306: P21-C312G-protein coupled receptors signature: T110-I126 MOTIFS 8 7477940CD1 310T19 T79 T234 N5 7 transmembrane receptor (rhodopsin family): G41-HMMER_PFAM T289 T308 Y288 TRANSMEMBRANE DOMAINS: H22-I50, P59- TMAP R84,L92-S1 18, L136-T164, D192-T220, H244-5264, D269-T289 N terminus isnon-cytosolic. - G-protein coupled receptors proteins BL00237: K91-BLIMPS_BLOCKS P 130, G232-V258, T280-K296 G-protein coupled receptorssignature: F103-A148 PROFILESCAN Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: F26-150, M60-K81, L105-I127, T141-A162, M200-L223, A237-R261, K270-K296 Olfactory receptor signaturePR00245: M60-K81, BLIMPS_PRINTS F178-D192, L238-G253, L272-L283,T289-Q303 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: V247-T308 RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L167-M246 G-PROTEIN COIJPLEDRECEPTORS BLAST_DOMO DM00013|S29710|15-301: F28-L302DM00013|P23275|17-306: H22-L302 DM00013|P30955|18-305: Q24-L302DM00013|P23266|17-306: Q24-L302 G-protein coupled receptors signature:A111-I127 MOTIFS 9 7477944CD1 309 S52 S65 583 S222 N6 N87 7transmembrane receptor (rhodopsin family): G39- HMMER_PFAM S301 S307 T76Y285 T286 Y85 TRANSMEMBRANE DOMAINS: V31-F59, F100- TMAP V122, I133-116,H191-I219, E233-I253, L263-L283 N terminus is cytosolic. G-proteincoupled receptors proteins BL00237: K88- BLIMPS_BLOCKS P127, L210-Y221,E229-V255, T277-K293 Visual pigments (opsins) retinal binding site:V255- PROFILESCAN S307 Olfactory receptor signature PR00245: M57-K78,BLIMPS_PRINTS P175-N 189, L235-1250, V269-L280, T286-C300 RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-I242 OLFACTORY RECEPTORPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD149621: T243-K303 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|S29710|15-301: L15-L299 DM00013|P23266|17-306:L15-L299 DM00013|P23274|18-306: Q22-C300 DM00013|S51356|18-307: L15-I29610 7480405CD1 315 S71 S97 S192 S197 N3 N9 Signal Peptide: M19-S44,M19-N46 HMMER S295 T11 T310 7 transmembrane receptor (rhodopsin family):G45- HMMER_PFAM Y294 TRANSMEMBRANE DOMAINS: L30-H58, L59- TMAP S79,Q104-Y127, M140-M168. T201-V229 E236- M264 N terminus is non-cytosolic.G-protein coupled receptors proteins BL00237: N94- BLIMPS_BLOCKS P133,L211-Y222, K239-L265, T286-M302 G-protein coupled receptors signature:F106-S150 PROFILESCAN Olfactory receptor signature PR00245: M63-K84,BLIMPS_PRINTS FLS i-D195, F242-G257, V278-L289, S295-I309 OLFACTORYRECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: T250-F313 RECEPTOR OLFACTORYPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD000921: F172-L249 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P23275|17-306: S25-L309 DM00013|P30954|29-316:V34-L305 DM00013|A57069|15-304: S25-L309 DM00013|S51356|18-307: S25-L305G-proein coupled receptors signature: S114-I130 MOTIFS Leuci ne zipperpattern: L191-L212 MOTIFS 11 7482486CD1 312 S67 S137 5188 N5 N42 7transmembrane receptor (rhodopsin family): W41- HMMER_PFAM S291 Y290TRANSMEMBRANE DOMAINS: N5-G25, S33- TMAP S53, T57-V76, M136-M164,L194-I221, E232-M260. M273-I288 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: K90- BLIMPS_BLOCKS P129, L207-Y218,K235-L261, T282-T298 G-protein coupled receptors signature: Y102-S146PROFILESCAN Signal peptides: MI-P24 SPSCAN Olfactory receptor signaturePR00245: M59-K80, BLIMPSPRINTS F177-D191, F238-G253, S274-L285,S291-L305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: F168-I245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD 149621: T246-L305 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|P23275|17-306: H23-L305DM00013|A57069|15-304: F18-L305 DM00013|P23274|18-306: L30-L305DM00013|P30954|29-316: H23-L301 Leucine zipper pattern: L187-L208 MOTIFSG-protein coupled receptors signature: A110-I126 MOTIFS 12 7482535CD1309 S84 S190 S237 N5 NISS N265 7 transmembrane receptor (rhodopsinfamily): G41- HMMER_PFAM S291 T78 Y290 TRANSMEMBRANE DOMAINS: F17-I45,T59- TMAP S75, K89-M117, Y132-N155, D193-I221, A232- L260, N270-P287 Nterminus is non-cytosolic. G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS L207-Y218, K235-Q261, I282-K298, N90-P129 Rhodopsin-likeGPCR superfamily signature BLIMPS_PRINTS PR00237: I26-N50, T59-K80,Y104-I126, L199-M222, S237-Q261, K272-K298 Olfactory receptor signaturePR00245: T59-K80, BLIMPS_PRINTS F177-N191, F238-G253, A274-L285,S291-G305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCGPROTEIN MULTIGENE FAMILY PD000921: L166-L245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCGPROTEIN MtJLTIGENE FAMILY PD 149621: T246-K307 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S51356|18-307: Q20-L301DM00013|P37067|17-306: L27-K302 DM00013|S29709|11-299: L27-G305DM00013|P23266|17-306: 126-I304 13 7482770CD1 312 S67 S93 S224 S229 N5N65 N195 Signal Peptides: M1-L55, M34-L55 SPSCAN S268 S291 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM Y290TRANSMEMBRANE DOMAINS: L23-S51, P58- TMAP L82, M95-F123, M136-M164,L198-5219, S243- T261 N terminus is non-cytosolic. G.protein coupledreceptors proteins BL00237: K90- BLIMPS_BLOCKS P129, G207-Y218,Q235-T261, T282-K298 G-protein coupled receptors signature: Y102-T148PROFILESCAN Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: F26-S50, M59-K80, S104-V126, L140- S161, I199-A222, A91-L115,S272-K298 Olfactory receptor signature PR00245: L238-G253, BLIMPS_PRINTSA274-L285, S291-L305, M59-K80, F177-D191 OLFACTORY RECEPTOR PROTEINGPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD149621: S246-R307 REc ORb ACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23265|17-306: E19-L305DM00013|P23268|18-307: S18-L305 DM00013|P30953|18-306: P21-L305DM00013|P30955|18-305: D20-L301 G-protein coupled receptors signature:L110-V126 MOTIFS 14 7475695CD1 325 S83 S193 S198 N10 N191 7transmembrane receptor (rhodopsin family): E46- HMMER_PFAM S275 T14 T43Y295 TRANSMEMBRANE DOMAINS: F22-I50, K62- TMAP P84, Q105-Y128,G151-I179, M202-I230, F243- T263, 5275-Y295 N terminus is non-cytosolic.G-protein coupled receptors proteins BL00237: K95- BLIMPS_BLOCKS P134,I212-Y223, Q240-R266, V287-K303 G-protein coupled receptors signature:Y107-G152 PROFILESCAN Olfactory receptor signature PR00245: M64-K85.BLIMPS_PRINTS Y182-D196, F243-S258, V279-L290, C296-I310 RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L171-L250 OLFACTORY RECEPTORPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD 149621: T251-I310 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM000|31P23270|18-311: F22-H311 DM000|31P23267|20-309:F22-I310 DM000|31P23274|18-306: P23-I310 DM000|31P30954|29-316: Q29-I310G-protein coupled receptors signature: T115-I131 MOTIFS 15 7477365CD1312 S67 S188 S291 T38 N5 N65 7 transmembrane receptor (rhodopsinfamily): D41- HMMER_PFAM T109 Y290 TRANSMEMBRANE DOMAINS: L33-F61, L130-TMAP A147, L198-Q226, K272-L288 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: K90- BLIMPS_BLOCKS P129, Y235-Q261,I282-K298 Olfactory receptor signature PR00245: Y177-D191, BLIMPS_PRINTSF238-G253, L274-L285, S291-I305, M59-K80 RECEPTOR OLFACTORY PROTEINGPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L166-L245 OLFACTORY RECEPTOR PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD149621: T246-1305 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|S51356|18-307: L17-R303 DM00013|P37067|17-306: L17-L304DM00013|S29709|11-299: T18-I305 DM00013|P23274|18-306: F28-I305 167479899CD1 324 S67 S232 S267 N5 N65 N89 Signal Peptide: M34-S53 HMMERS291 T170 T188 Signal Peptide: M34-L55 SPSCAN T300 7 ransmembranereceptor (rhodopsin family): G41- HMMER_PFAM Y290 TRANSMEMBRANE DOMAINS:S33-S53, P58- TMAP I78, S95-Y123, R131-T151, A156-L176, D191-T219,V238-S261 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: R90- BLIMPS_BLOCKS P129, H235-S261, P282-K298G.protein coupled receptors signature: F103-L147 PROFILESCAN Olfactoryreceptor signature PR00245: M59-K80, BLIMPSPRINTS F177-D191, V238-G253,A274-V285, S291-I305 Melanocortin receptor family signature PR00534:BLIMPSPRINTS I126-N137, S51-L63 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANB GLYCOPROTEIN MULTIGENE FAMILYPD000921: L166-L245 OLFACTORY PROTEIN 19 GPROTEIN COUPLED BLAST_PRODOMRECEPTOR TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY OLFACTION P0048705:M1-H54 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: S246-R307G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23265|17-306: I18-K303DM00013|P23268|18-307: E19-I305 DM00013|S29707|18-306: P21-L301DM00013|P30955|18-305: D20-I305 G-protein coupled receptors signature:L110-I126 MOTIFS Leucine zipper pattern. L143-L164 MOTIFS 17 7480412CD1314 S65 S91 S186 S191 N3 N184 7 transmembrane receptor (rhodopsinfamily): G39- HMMER_PFAM S289 Y288 TRANSMEMBRANE DOMAINS: H21-C49, L53-TMAP 573, Q98-Y121, M134-I160, E194-I219, E230-M258 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: N88-BLIMPS_BLOCKS P127, L205-Y2 16, K233-L259, T280-M296 G-protein coupledreceptors signature: F100-S144 PROFILESCAN Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: L24-H48, M57-K78,Y102-1124, M197-L220, M270-M296 Olfactory receptor signature PR00245:V272-V283, BLIMPS_PRINTS 5289-L303, M57-K78, F175-D189, F236-G251OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPRQTEIN MULTIGENE FAMILY PD149621: T244-L303 RECEPTOR OLFACTORYPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD000921: F166-L243 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P23275|17-306: S19-L303 DM00013|P30954|29-316:V28-L299 DM00013|P23266|17-306: L15-L303 DM00013|A57069|15-304: S19-L303Leucine zipper pattern: L185-L206 MOTIFS G-protein coupled receptorssignature: S108-I124 MOTIFS 18 7485460CD1 314 S65 S186 S289 T76 N3 N63N153 N261 7 transmembrane receptor (rhodopsin family): G39- HMMER_PFAMT161 T268 Y288 TRANSMEMBRANE DOMAINS: L21-L49, P56- TMAP Y71, F89-A117,T133-T161, S193-I221, M266-V287 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: I280- BLIMPS_BLOCKS K296, K88-P127,F207-F218 G-protein coupled receptors signature: F100-C149 PROFILESCANOlfactory receptor signature PR00245: M57-K78, BLIMPS_PRINTS F175-D189,F236-G251, A272-L283, S289-V303 Signal peptide: M43-A108 SPSCAN RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-L243 OLFACTORY RECEPTORPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD149621: T244-K305 OLFACTORY RECEPTOR PROTEiN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD002495: M1-S51 0-PROTEiN COUPLED RECEPTORS BLAST_DOMODM00013|551356|18-307: L15-A298 DM00013|S29709|11-299: T16-G304DM00013|P37067|17-306: L15-K301 DM00013|P23266|17-306: L15-V303G-protein coupled receptors signature: A108-L124 MOTIFS 19 7472173CD1312 S65 S182 S191 N3 N63 7 trarismembrane receptor (rhodopsin family):G39- HMMER_PFAM 5265 T135 T289 Y288 TRANSMEMBRANE DOMAINS: L12-N40, Q54-TMAP T73, V75-C95, F100-R120, K137-P165, I192-L220, S237-R259 N terminusiscytosolic. G-protein coupled receptors proteins BL00237: T88-BLIMPS_BLOCKS P127, Q233-R259, T280-K296 SignalPeptide: M1-A49 SPSCANG-protein coupled receptors signature: F100-S145 PROFILESCAN Olfactoryreceptor signature PR00245: M57-K78, BLIMPS_PRINTS F175-D189, F236-G251,V272-L283, T289-M303 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-L243OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD 149621: T244-M303 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|P23267|20-309: F15-M303DM00013|P23270|18-311: F15-M303 DM00013|P30955|18-305: Q22-M303DM00013|P37067|17-306: G20-K301 G-protein coupled receptors signature:T108-I124 MOTIFS 20 7475690CD1 312 S67 S93 S232 S291 N5 N42 N65 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM T78 T163 T305Y290 TRANSMEMBRANE DOMAINS: W23-M43, T51- TMAP F71, A95-H123, T135-T163,L199-R227, G233-R261 N terminus is non-cytosolic. G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS N282-K298, K90-P129, S232-M258G-protein coupled receptors signature: F102-G152 PROFILESCAN Olfactoryreceptor signature PR00245: M59-K80, BLIMPS_PRINTS F177-N191, F238-G253,A274-L285, S291-T305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I246OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V248-K303 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S29709|11-299: L27-K303DM00013|P37067|17-306: L27-T305 DM00013|S51356|18-307: L27-A300DM00013|P23266|17-306: S18-K303 G-protein coupled receptors signature:T110-I126 MOTIFS 21 7476068CD1 318 S56 S151 T53 T169 N5 7 transmembranereceptor (rhodopsin family): G43- HMMER_PFAM T179 T263 Y62 Y294 SignalPeptide: M27-A85 SPSCAN TRANSMEMBRANE DOMAINS: P32-L52, M67- TMAPTRANSMEMBRANE DOMAINS: P32-L52, M67- F87, L103-P131, C147-Q172,I196-I223, A239- T263, Q264-I292 N terminus is non-cytosolic. G-proteincoupled receptors proteins BL00237: BLIMPS_BLOCKS V209-Y220. H237-T263,P286-Q302, G92- P131 Olfactory receptor signature PR00245: M61-Q82,BLIMPSPRINTS T179-D193, L240-G255, H11-L22 G-PRQTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|G45774|18-309: P20-E303 DM00013|P23272|18-306:Q25-L309 DM00013|S29707|18-306: Q23-Q302 DM00013|P23273|18-306: D24-L30922 7476163CD1 314 S67 5308 T288 N5 N65 7 transmembrane receptor(rhodopsin family): G41- HMMER_PFAM Y287 TRANSMEMBRANE DOMAINS: E22-T50,M59- TMAP I83, Q100-A125. R138-L166, T194-L222, A236- Y256, P266-1286 Nterminus is non-cytosolic. G-protein coupled receptors proteins BL00237:K90- BLIMPS_BLOCKS P129, R234-R260, S279-K295 G-protein coupledreceptors signature: F102-G151 PROFILESCAN Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: V26-T50, M59-K80,F104-I126. M199-L222, A236-R260, T269-K295 Olfactory receptor signaturePR00245: M59-K80, BLIMPS_PRINTS F177-D191, I237-V252, I271-L282.T288-K302 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I244G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|S29710|15-301: I17-L301DM00013|P23266|17-306: I17-L301 DM00013|P23275|17-306: I17-L301DM00013|P30955|18-305: L27-L301 G-protein coupled receptors signature:A110-I126 MOTIFS 23 7476166CD1 311 S67 S87 5308 T288 N5 N65 7transrnembrane receptor (rhodopsin family): G41- HMMER_PFAM Y287 SignalPeptide: M1-T38 SPSCAN TRANSMEMBRANE DOMAINS: T18-M46, M59- TMAP S87,N95-Y123, C141-C169, V184-F212, R233-P261 N terminus is non-cytosolic.G-protein coupled receptors proteins BL00237: K90- BLIMPS_BLOCKS P129,R234-R260, S279-K295 G-protein coupled receptors signature: F102-A147PROFILESCAN Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: V26-T50, M59-K80, F104-I126, H140- S161-M199-L222, A236-R260,K269-K295 Olfactory receptor signature PR00245: T288-K302, BLIMPS_PRINTSM59-K80, F177-D191, I237-V252, I271-L282 RECEPTOR OLFACTORY PROTEINGPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L166-I244 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|S29710|15-301: L17-L301 DM00013|P23266|17-306: L17-L301DM00013|P23275|17-306: L17-L301 DM00013|P30953|18-306: Q19-L301G-protein coupled receptors signature: V110-I126 MOTIFS 24 7476686CD1312 S67 S137 S230 N5 N65 N268 7 transmembrane receptor (rhodopsinfamily): G41- HMMER_PFAM S267 T50 T78 Y287 T288 TRANSMEMBRANE DOMAINS: F17-145, P58- TMAP 183, Q100-Y123, K139-P167, T194-L222, L237- L265 Nterminus is non-cytosolic. G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS H231-I257, T279-Q295, K90-P129 G-protein coupled receptorssignature: F102-L147 PROFILESCAN Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: F26-T50, L59-K80, M104-I126, L140-V161, V199-L222, A236-W260, K269-Q295 Olfactory receptor signaturePR00245: L59-K80, BLIMPS_PRINTS I177-E191, L237-G252, L271-L282,T288-R302 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V246-L301 G-PROTEIN DOUPLEDRECEPTORS BLAST_DOMO DM00013|S29710|15-301: F28-L301DM00013|P30955|18-305: F27-L301 DM000I3|P23269|15-304: E22-1298DM00013|P23274|18-306: E22-I298 G-protein coupled receptors signature:A110-I126 MOTIFS 25 7477363CD1 324 S67 S88 S106 S137 N5 N52 N65 7transmembrane receptor (rhodopsin family): 041- HMMER_PFAM S188 S227S291 Y290 T78 T163 T270 Signal Peptide: M1-Q56 SPSCAN Y310 TRANSMEMBRANEDOMAINS: L23-I51, Y95- TMAP Y123, R138-L166, L197-V225, G232-Y259, T270-K295 N terminus is non-cytosolic. G-protein coupled receptors proteinsBL00237: K90- BLIMPS_BLOCKS P129, S235-Q261, F282-K298 G-protein coupledreceptors signature: F102-F150 PROFILESCAN Olifactory receptor signaturePR00245: M59-K80, BLIMPS_PRINTS F177-D191, F238-G253, V274-F285,S291-L305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I246OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V248-R307 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|P37067|17-306: T18-L304DM00013|S51356|18-307: L23-L301 DM00013|529709|11-299: T18-L305DM00013|P23266|17-306: L27-L305 G-protein coupled receptors signature:A110-I126 MOTIFS 26 7477368CD1 325 S29 S77 S147 S243 N15 N75 7transmembrane receptor (rhodopsin family): G5 I- HMMER_PFAM S307 S312S318 Y297 T88 T234 T298 TRANSMEMBRANE DOMAINS: 528-V56, M69- TMAP Y306R97, E105-Y133. M146-V174, T202-I230, S248- W270 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: P36-BLIMPS_BLOCKS A47, G241-I267, T289-K305, K100-P139 G-protein coupledreceptors signature: F112-L157 PROFILESCAN Olfactory receptor signaturePR00245: M69-K90, BLIMPS_PRINTS F187-D201, L247-G262, L281-L292,T298-S312 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: T255-F316 RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L176-H253 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S29710|15-301: F38-L311DM00013|P30955|18-305: I35-L311 DM00013|P23274|18-306: I35-M308DM00013|P23266|17-306: L27-L311 G-protein coupled receptors signature:A120-I136 MOTIFS 27 7480408CD1 317 S67 S88 S137 S188 N5 7 transmembranereceptor (rhodopsin family): S41- HMMER_PFAM S193 S229 S291 Y290NADH-Ubiquinone/plastoquinone (complex 1): D11- HMMER_PFAM S38TRANSMEMBRANE DOMAINS: A21-L48, Q100- TMAP Y123, Y132-T160, C203-S229,E232-Y259 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: R90- BLIMPS_BLOCKS P129, L207-Y218, G235-L261,T282-T298 G-procein coupled receptors signature: F102-A147 PROFILESCANSignal Peptide: M1-A40 SPSCAN Rhodopsin-like GPCR superfamily signatureBLIMPS_PRINTS PR00237: L26-H50, M59-K80, Y104-I126, L26-I47, M199-L222,F23-I47, K272-T298 Olfactory receptor signature PR00245: M59-K80,BLIMPS_PRINTS F177-D191, V238-G253, V274-L285, S291-V305 OLFACTORYRECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V247-R307 RECEPTOR 6LFACTORYPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD000921: F168-V246 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P23275|17-306: L26-G306 DM00013|P23266|17-306:L26-V305 DM00013|P23274|18-306: L26-V305 DM00013|P30955|18-305: L26-V305G-protein coupled receptors signature: A110-I126 MOTIFS 28 74804O9CD1312 S65S83 S186 S289 N3 N63 7 transmembrane receptor (rhodopsin family):G39- HMMER_PFAM T6 T47 Y288 TRANSMEMBRANE DOMAINS: L11-L34, H54- TMAPC70, K92-R 120, V134-F162. V195-V223, R232- P260 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237:BLIMPS_BLOCKS T233-R259, P280-K296, T88-P127 G-proein coupled receptorssignature: F100-A145 PROFILESCAN Visual pigments (opsins) retinalbinding site: P261- PROFILESCAN V312 Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: L24-T48, M57-T78. V102-V124, H242-1263. 1197-F220, F60-L84. L270-K296 Olfactory receptor signaturePR00245: M57-T78, BLIMPS_PRINTS F175-D 189, F236-S251, L272-F283,S289-M303 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MLJLTIGENE FAMILY PD000921: L164-L244G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23273|18-306: I23-M303DM00013|S29709|11-299: F29-M303 DM00013|P23272|18-306: Q22-M303DM00013|P23266|17-306: F29-M303 29 7482487CD1 316 S5 S64 S190 S288 N3 7transmembrane receptor (rhodopsin family): A38- HMMER_PFAM Y287SignalPeptide: M1-A38 SPSCAN TRANSMEMBRANE DOMAINS: L15-I43, S61- TMAPD81, C94-L114, C138-T157, T194-1222, E229-Y256 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: K87-BLIMPS_BLOCKS P126, L204-Y215, K232-L258, T279-I295 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: I23-Q47, M56-K77,Y101-V123, M196-L219, K269-I295 Olfactory receptor signature PR00245:V271-L282, BLIMPS_PRINTS S288-F302, M56-K77, F174-D 188, F235-G250RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: Y165-L242 OLFACTORY RECEPTORPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD 149621: T243-V301 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|P23275|17-306: I23-V301 DM00013|S29709|11-299:V24-K300 DM00013|P30954|29-316: V24-V294 DM00013|P23270|18-311: I23-K30030 7485424CD1 314 T83 T168 T193 N10 7 transmembrane receptor (rhodopsinfamily): G46- HMMER_PFAM T275 Y295 TRANSMEMBRANE DOMAINS: M30-T58, L68-TMAP G88, S98-L118, D126-C146, V150-R170. R198- M224, E237-Y264,K277-5296 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: N95- BLIMPS_BLOCKS P134, F212-Y223, E237-M263,I287-K303 G-protein coupled receptors signature: L110-V152 PROFILESCANRhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:P31-R55, M64-K85, F109-I131, F199- P220, 1204-1227, A242-Q266, K277-K303Olfactory receptor signature PR00245: M64-K85, BLIMPS_PRINTS F182-D196,F243-G258, A279-L290, S296-I310 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD000921: L171-L251 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD 149621: V253-K313G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|S51356|18-307: L22-I311DM00013|P37067|17-306: L22-I309 DM00013|S29709|11-299: T23-I310DM00013|P23274|18-306: T23-I310 G-protein coupled receptors signature:S115-I131 MOTIFS 31 7475196CD1 321 S110 S232 S295 N6 N44 Signal Peptide:M67-G85 HMMER S314 7 transmembrane receptor (rhodopsin family): G43-HMMER_PFAM Y294 TRANSMEMBRANE DOMAINS: L25-T53, M61- TMAP F89,M146-K166, S173-S193, Y200-Y220, A239- G267, P271-I292 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: R92-BLIMPS_BLOCKS P131, F253-H264, Q234-L260, P286-R302 Olfactory receptorsignature PR00245: M278-M289, BLIMPS_PRINTS M61-T82, A179-S 193,L240-I255 PUTATIVE GPROTEIN COUPLED RECEPTOR BLAST_PRODOM RAIC PD170483:I247-Q310 G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P34982|17-305:F33-I301 DM00013|S29708|18-306: I36-K307 DM00013|G45774|18-309: H26-Q303DM00013|P23274|18-306: F33-K307 G-protein coupled receptors signature:M112-V128 MOTIFS 32 7475295CD1 311 S52 567 S137 S291 N5 N195 N206 7transmembrane receptor (rhodopsin family): A41- HMMER_PFAM T8 T193 T204Y290 TRANSMEMBRANE DOMAINS: P21-I49, Q100- TMAP F123, L144-N172,L198-L226, K272-I289 N terminus is cytosolic. G-protein coupledreceptors signature: Y102-S146 PROFILESCAN Olfactory receptor signaturePR00245: M59-K80, BLIMPS_PRINTS F177-D191, F238-G253, A274-L285,S291-M305 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: I166-L245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: T246-K308 OLFACTORY RECEPTORPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD002495: E4-553 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|S51356|18-307: L17-L301 DM00013|P37067|17-306: L17-V304DM00013|S29709|11-299: S18-G306 DM00013|P23266|17-306: L17-M305G-protein coupled receptors signature: T110-I126 MOTIFS 33 7478361CD1311 S7 s49 S67 5266 N5 N264 7 transmembrane receptor (rhodopsin family):G41- HMMER_PFAM T6 T290 Y289 TRANSMEMBRANE DOMAINS: I31-H56, Q100- TMAPY123, A145-L173, V200-K228, F237-T257 E269- Y289 N terminus iscytosolic. G-protein coupled receptors proteins BL00237: R90-BLIMPS_BLOCKS P129, V206-Y217. R234-Q260, T281-K297 G-protein coupledreceptors signature: F102-A147 PROFILESCAN Olfactory receptor signaturePR00245: M59-Q80, BLIMPS_PRINTS F176-D190, F237-G252, V273-L284,T290-L304 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: M166-L245OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: V246-R306 G-PROTE1N COUPLEDRECEPTORS BLAST_DOMO DM00013|P23275|17-306: 518-L304DM00013|A57069|15-304: F17-L304 DM00013|P30953|18-306: P21-L304DM00013|P30955|18-305: L27-L304 G-protein coupled receptors signature:.T110-V126 MOTIFS 34 7482534CD1 312 S52 S67 S93 S227 N42 N65 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM T289 C250,P281-Y288 TRANSMEMBRANE DOMAINS: F31-H56, P58- TMAP Y84, K95-F123,P129-G 152, Q196-I221, E232- Y259, P266-N284 N terminus isnon-cytosolic. G-protein coupled receptors proteins BL00237: R90-BLIMPS_BLOCKS P129, E232-V258, G280-K296 G-protein coupled receptorssignature: F102-T148 PROFILESCAN Olfactory receptor signature PR00245:M59-K80, BLIMPS_PRINTS F177-D191, F238-G253, V272-L283, T289-L303Melanocortin receptor family signature PR00534: BLIMPS_PRINTS S51-L63,I126-N137 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I246G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23275|17-306: P18-L303DM00013|P30953|18-306: F28-H304 DM00013|P30955|18-305: F28-L303DM00013|S29707|18-306: F28-I302 35 7490493CD1 314 S67 S291 T87 T232 N5N52 N65 N256 Signal Peptide: M40-S74 SPSCAN T270 7 transmembranereceptor (rhodopsin family): G41- HMMER_PFAM Y290 TRANSMEMBRANE DOMAINS:Q4-Q24, F31- TMAP L51, P58-T78, Q100-F123, M136-5164, E196-R220 Nterminus is cytosolic. G-protein coupled receptors proteins BL00237:T90- BLIMPS_BLOCKS P129, V207-Y218, A188-I214, T282-K298 G-proteincoupled receptors family 2 proteins BLIMPS_BLOCKS BL00649: I34-P79,Y198-K227, L280-W305 G-protein coupled receptors signature: Y102-F147PROFILESCAN Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: A199-L222, F193-5217, K272-K298, Q26-S50, M59-E80, I104-I126,V140-S161 Olfactory receptor signature PR00245: M59-E80, BLIMPS_PRINTSI177-D191, P238-0253, I274-L285, S291-W305 RECEPTOR OLFACTORY PROTEINGPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD00092 1: F168-L245 OLFACTORY RECEPTOR PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD149621: T246-K308 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P30954|29-316: 518-K303 DM00013|P23269|15-304: P21-L304DM00013|P30955|18-305: P21-L301 DM00013|S29707|18-306: P21-K298G-protein coupled receptors signature: T110-I126 MOTIFS 36 58001274CD1393 S147 S347 S371 N86 N101 7 transmembrane receptor (rhodopsin family);G121- HMMER_PFAM T57 T88 Y370 TRANSMEMBRANE DOMAINS: L97-M125, G171 TMAPL195, V274-L302, G313-R341 N terminus is cytosolic. G-protein coupledreceptors proteins BL00237: BLIMPS_BLOCKS K170-5209, I105-F116,E312-T338, T362-L378 G-protein coupled receptors signature: F182-G226PROFILESCAN Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: F106-H130, M139-K160, F184-I206, M220-V241,V279-L302,A317-R341, K352-L378 Olfactory receptor signature PR00245:M139-K160, BLIMPS_PRINTS F257-D271, F318-A333, L354-L365, S371-F385OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD149621: T326-G386 RECEPTOR OLFACTORYPROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEINMULTIGENE FAMILY PD000921: I246-L325 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|S297071|18-306: L98-F385 DM00013|P232661|17-306:L107-V384 DM00013|A570691|15-304: I111-G386 DM00013|P309551|18-305:L98-V384 G-protein coupled receptors signature: 5190-I206 MOTIFS 377476809CD1 314 S67 S291 T87 T232 N5N65 Signal Peptide: M1-A43 HMMER T2707 transmembrane receptor (rhodopsin family): G41- HMMER_PFAM Y290TRANSMEMBRANE DOMAINS: Q26-554, P58- TMAP V84, Q100-F123, M136-S164,E196-R220 N terminus is non-cytosolic. G-protein coupled receptorsproteins BL00237: T90- BLIMPS_BLOCKS P129, 1207-Y2 18, A 188-I2 14,T282-K298 G-protein coupled receptors signature: Y 102-F 147 PROFILESCANRhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:Q26-S50, M59-E80, I104-I126, A199-L222, F193-5217, K272-K298 Olfactoryreceptor signature PR00245: I177-D191 BLIMPS_PRINTS F238-G253,M274-L285, S291-W305, M59-E80 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD000921: F168-L245 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN1 MULTIGENE FAMILY PD149621: T246-R308G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|P23269|15-304: P21-L304DM00013|S29707|18-306: P21-L301 DM00013|P30955|18-305: Q24-L304DM00013|P23274|18-306: E22-L304 G-protein coupled receptors signature:A110-I126 MOTIFS 38 7476048CD1 327 S95 S110 S295 T53 N5 N6 N209 SignalPeptide: M1-C24 HMMER T139 T270 T300 Signal Peptide: M46-G85 SPSCAN 7transmembrane receptor (rhodopsin family): G43- HMMER_PFAM V149,V213-Y294 TRANSMEMBRANE DOMAINS: P32-I52, Y63- TMAP V83. K97-F125,L138-N166, S197-R225, A239- F267, R272-I292 N terminus is non-cytosolic:G-protein coupled receptors proteins BL00237: R92- BLIMPS_BLOCKS P131,F253-H264, K234-L260, P286-R302 G-protein coupled receptors signature:F104-R153 PROFILESCAN Olfactory receptor signature PR00245: M61-T82,BLIMPS_PRINTS L240-V255, S295-L309 PUTATIVE GPROTEIN COUPLED RECEPTORBLAST_PRODOM RAIC PD170483: 1247-L308 G-PROTEIN COUPLED RECEPTORSBLAST_DOMO DM00013|G45774|18-309: P20-M305 DM00013|I45774|28-318:V33-M305 DM00013|P34982|17-305: L36-L309 DM00013|P23266|17-306: L36-L309G-protein coupled receptors signature: L112-I128 MOTIFS 39 7476679CD1319 S7 S18 S49 S193 N5 7 transmembrane receptor (rhodopsin family): G41-HMMER_PFAM T266 T291 Y290 TRANSMEMBRANE SEGMENTS: P21-S49 P58- TMAP W86C127-G152 M197-V225 E232-Y259 G-protein coupled recept BL00237:K90-P129, V207- BLIMPS_BLOCKS Y218, R235-Q261, T282-K298 G-proteincoupled receptors signature PROFILESCAN g_protein_receptor.prf:Y102-A147 Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: V26-H50, M59-Q80, S104-I126, M199- A222, A237-Q261, K272-K298Olfactory receptor signature PR00245: M59-Q80, BLIMPS_PRINTS F177-D191,F238-G253, 1274-L285, T291-V305 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD000921: L166-V245, PD149621: V247-V305 G-PROTEIN COUPLED RECEPTORSDM00013 BLAST_DOMO P23275|17-306: S18-V305 A57069|15-304: F17-V305P30955|18-305: P21-V305 S29707|18-306: P21-L301 G-protein coupledreceptors signature T110-I126 MOTIFS 40 7486996CD1 308 S67 S232 S263 N5N65 signal_cleavage: M1-G41 SPSCAN T291 7 transmembrane receptor(rhodopsin family): G41- HMMER_PFAM Y290 TRANSMEMBRANE SEGMENTS: F17-I45H56- TMAP T75 L99-R122 M136-5164 A194-I222 N-terminus non-cytosolicG-protein coupled recept BL00237: Q90-P129, S235- BLIMPS_BLOCKS R261,T282-R298 G-protein coupled receptors signature PROFILESCANg_protein_receptor.prf: Y102-L146 Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: S26-S50, M59-K80, V104-I126, A199-1222, K272-R298 Olfactory receptor signature PR00245: M59-K80,BLIMPS_PRINTS F177-N191, F238-G253, V274-L285, T291-W305 RECEPTOROLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245,T246-K308 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMO P23267|20-309:Fl 7-K306 P23270|18-311: F17-L301 S51356|18-307: L23-L301 P47881|20-309:L14-L301 G-protein coupled receptors signature; T110-I126 MOTIFS 417490489CD1 310 S290 N4 7 transmembrane receptor (rhodopsin family): G40-HMMER_PFAM Y289 TRANSMEMBRANE SEGMENTS: Q17-L45 H55- TMAP S71 V90-C118M135-L163 V196-I224 S238-A260 N-terminus non-cytosolic G-protein coupledrecept BL00237: K89-P128, L206- BLIMPS_BLOCKS Y217, R234-A260, N281-K297G-protein coupled receptors signature PROFILESCANg_protein_receptor.Prf: F101-T146 Olfactory receptor signature PR00245:M58-K79, BLIMPS_PRINTS F176-D190, F237-G252, L273-L284, S290-L304RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: L165-L244, PD149621: V246-Q307G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMO P23275|17-306: P20-L304A57069|15-304: F16-L304 P23266|17-306: P20-L304 S51356|18-307: P20-R302Leucine zipper pattern L24-L45 MOTIFS G-protein coupled receptorssignature T109-I125 MOTIFS 42 7475304CD1 312 S137 S290 T8 T49 N5 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM T160 T269Y298 Y289 TRANSMEMBRANE SEGMENTS: T18-I46 Y95- TMAP Y123 M136-F164F202-L222 R233-T253 K271- L287 N-terminus cytosolic G-protein coupledrecept BL00237: I281-K297, N90- BLIMPS_BLOCKS P129, Q234-Q260 Olfactoryreceptor signature PR00245: M59-K80, BLIMPS_PRINTS F177-N191, F237-G252,A273-L284, S290-W304 RECEPTOR OLFAGTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L244,PD149621: T245-R302 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMOS51356|18-307: I17-R302 S29709|11-299: T18-T303 P37067|17-306: I17-R302P23266|17-306: Q24-R302 43 7475248CD1 314 S8 S67 S87 S167 N5 N65 N73N159 signal_cleavage: M1-T38 SPSCAN S188 S291 S306 7 transmernbranereceptor (rhodopsin family): 041- HMMER_PFAM S311 T2 T78 T310 Y290TRANSMEMBRANE SEGMENTS: Q24-I51 F104- TMAP A124 S133-L153 I198-F226A237-Y257 L268-L288 N-terminus cytosolic G-protein coupled receptBL00237: H235-R261, I282- BLIMPS_BLOCKS K298, K90-P129, I207-Y218Olfactory receptor signature PR00245: M59-K80, BLIMPS_PRINTS F177-D191,F238-A253, A274-L285, S291-I305 RECEPTOR OLFACTORY PROTEIN GPROTEINBLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILYPD000921: L166-L245, PD149621: T246-S311, PD002495: K4-S53 G-PROTEINCOUPLED RECEPTORS DM00013 BLAST_DOMO S51356|18-307: E22-L301P37067|17-306: L17-L301 S29709|11-299: L23-I305 P23266|17-306: Q24-530644 7475191CD1 314 S7 S66 5232 S237 N4 N190 7 transmembrane receptor(rhodopsin family): G40- HMMER_PFAM T291 F290 TRANSMEMBRANE SEGMENTS:F30-Q55 V79- TMAP Y104 L130-W158 E196-S223 D269-K296 G-protein coupledrecept BL00237: Q90-P129, R235- BLIMPS_BLOCKS K261,T282-I298 G-proteincoupled receptors signature PROFILESCAN g_protein_receptor.prf:F102-V147 Olfactory receptor signature PR00245: M58-V79, BLIMPS_PRINTSF177-N191, F238-G253, V274-L285, T291-V305 RECEPTOR OLFACTORY PROTEINGPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L166-H244 G-PROTEIN COUPLED RECEPTORS DM00013BLAST_DOMO P23267|20-309: F16-K306 P23270|18-311: F16-R302P30954|29-316: L26-L301 P23274|18-306: P17-L301 G-protein coupledreceptors signature T110-V126 MOTIFS 45 7480413CD1 318 S176 5193 S296 N5N10 signal_cleavage: M1-556 SPSCAN T92 7 transmembrane receptor(rhodopsin family): G46- HMMER_PFAM Y295 TRANSMEMBRANE SEGMENTS: K27-I54H61- TMAP L87 Q105-Y128 V145-P172 M202-I230 R239-R267 M277-L293N-terminus cytosolic G-prolein coupled recept BL00237: D95-P134, L212-BLIMPS_BLOCKS Y223, R240-L266, T287-T303 G-protein coupled receptorssignature PROFILESCAN g_protein_receptor.prf: F107-A152 Rhodopsin-likeGPCR superfamily signature BLIMPS_PRINTS PR00237: L31-H55, M64-K85.H109-V131, V145- P166, T204-L227, A242-L266, M277-T303 Olfactoryreceptor signature PR00245: 5296-M310, BLIMPS_PRINTS M64-K85, F182-D196,L243-G258, V279-L290 RECEPTOR OLFACTORY PROThIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: F173-I251,PD149621: 1252-M310 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMOP23275|17-306: A24-M310 A57069|15-304: S26-M310 P30954|29-316: L32-L306S5I356|18-307: S26-L306 G-protein coupled receptors signature A115-V131MOTIFS Leucine zipper pattern L192-L213 MOTIFS 46 7476165CD1 314 S67 S87S93 S288 N5 N65 N274 signaLcleavage: M1-G41 SPSCAN S310 7 transmembranereceptor (rhodopsin family): G41- HMMER_PFAM Y287 TRANSMEMBRANESEGMENTS: R21-I49 N95- TMAP Y123 K138-F166 P193-I221 G232-R260N-terminus cytosolic G-protein coupled recept BL00237: K90-P129, N234-BLIMPS_BLOCKS R260, T279-K295 G-protein coupled receptors signaturePROFILESCAN protein_receptor.prf: F102-A147 Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: T269-K295, F26-T50,M59-K80, P104- I126. V140-I161,M199-L222, A236-R260 Olfactory receptorsignature PR00245: M59-K80, BLIMPS_PRINTS F177-D191. L237-V252,I271-L282, S288-Q302 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: F168-L245G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMO 529710|15-301: L17-L301P23266|17-306: L17-L301 P30955|18-305: F28-L301 P30953|18-306: E22-L301G-protein coupled receptors signature A110-I126 MOTIFS 47 7478345CD1 313S67 S138 S234 T8 N5 signal cleavage: M1-H56 SPSCAN T271 T292 7transmembrane receptor (rhodopsin family): G41- HMMER_PFAM Y29TRANSMEMBRANE SEGMENTS: L23-V51 Q101- TMAP Y124 H194-I222 S234-R262N-terminus non-cytosolic G-protein coupled recept BL00237: I208-Y219,R236- BLIMPS_BLOCKS R262, T283-R299, Q91-P130 G-protein coupledreceptors signature PROFILESCAN gprotein.receptor.prf: Y103-T148Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:P26-Q50. M59-R80, F105-I127, V200- L223, R273-R299 Olfactory receptorsignature PR00245: M59-R80, BLIMPS_PRINTS F178-G192, F239-A3254,L275-L286, T292-V306 OLFACTORY RECEPTOR PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD149621: V248-Q309,PD000921: L167-L247 0-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMOP23275|17-306: 518-V306 A57069|15-304: F17-V306 P30954|29-316: L27-L302S51356|18-307: P26-L302 G-protein coupled receptors signature S111-I127MOTIFS 48 7475245CD1 311 S52 S67 S137 5291 N5 N195 N206 7 transrnembranereceptor (rhodopsin family): R54- HMMER_PFAM T8 T193 T204 Y290TRANSMEMBRANE SEGMENTS: 518-T46 S53- TMAP M81 Q100-F123 V142-R170L198-L226 V270-L288 N-terminus non-cytosolic G-protein coupled receptBL00237: I282-N298, K90- BLIMPS_BLOCK P129 G-protein coupled receptorssignature PROFILESCAN g_protein_receptor.prf: Y102-Y149 Rhodopsin-likeGPCR superfamily signature BLIMPS_PRINTS PR00237: V59-K80, F104-I126,L199-L222, K272- N298 Olfactory receptor signature PR00245: V59-K80,BLIMPS_PRINTS F177-D191, F238-G253, A274-L285, S291-M305 RECEPTOROLFACTORY PROTEIN GPROTEIN BLAST_PRODOM COUPLED TRANSMEMBRANEGLYCOPROTEIN MULTIGENE FAMILY PD000921: F168-L245, PD149621: T246-K308,PD002495: E4-S53 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMOS51356|18-307: L17-L301 P37067|17-306: L17-V304 S29709|11-299: S18-G306P23266|17-306: L17-M305 G-protein coupled receptors signature T110-I126MOTIFS 49 7485481CD1 310 S65 S289 T16 T76 N3 N204 7 transmembranereceptor (rhodopsin family): G39- HMMER_PFAM T262 Y288 TRANSMEMBRANESEGMENTS: L21-I49 C99- TMAP A123 M134-Y162 K193-V221 N-terminuscytosolic Q-protein coupled recept BL00237: K88-P127, F151-BLIMPS_BLOCKS Y162, 1280-K296 G-protein coupled receptors signaturePROFILESCAN g_protein_receptor.prf: Y100-V145 Olfactory receptorsignature PR00245: M57-K78, BLIMPS_PRINTS F175-R189, F236-G251,V272-L283, 5289-I303 RECEPTOR OLFACTORY PROTEIN GPROTEIN BLAST_PRODOMCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-L243,PD149621: T244-Y307 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMOS51356|18-307: L15-K301 P37067|17-306: L15-K301 S29709|11-299: L21-I303P23274|18-306: E20-I303 50 7482835CD1 331 S13 S180 T195 N44 7transmembrane receptor (rhodopsin family): G43- HMMER_PFAM T265 V143TRANSMEMBRANE SEGMENTS: S24-R52 L65- TMAP A85 A101-A121 G144-R168N199-R227 A237-T265 P274-L299 N-terminus non-cytosolic G-protein coupledrecept BL00237: H92-P131, E236- BLIMPS_BLOCKS S262, P302-R318 Olfactoryreceptor signature PR00245: M61-K82, BLIMPS_PRINTS S180-V194, L242-I257Melanocortin receptor family signature PR00534: BLIMPS_PRINTS M53-L65,I116-A127 G-PROTEIN COUPLED RECEPTORS DM00013 BLAST_DOMO G45774|18-309:P20-L321 P23266|17-306: L29-Y256, A295-A326 S29710|15-301: L29-P258,Y298-L321 P47881|20-309: P20-Y256, L300-L321 51 7475100CD1 312 S20 5230S265 N5 N65 N307 7-transmembrane receptor (rhodopsin family): G41-HMMER_PFAM S303 T288 Y287 Transmembrane domains: S18-V46, M59-R87, F94-TMAP R122, P138-L166, M198-Q226, G231-Y258, H266- I286 N-terminus isnon-cytosolic. G-protein coupled receptor BL00237: K90-P129,BLIMPS_BLOCKS S18-L44, T279-M295 G-protein coupled receptors signature:F102-I147 PROFILESCAN Olfactory receptor signature PR00245: M59-K80,BLIMPS_PRINTS F177-E191, F237-G252, L271-L282, T288-C302 RECEPTOROLFACTORY PROTEIN RECEPTOR BLAST_PRODOM LIKE G PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-I245G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|S29710|15-301: D19-R300DM00013|P23275|17-306: L17-R300 DM00013|P23266|17-306: L17-R300DM00013|P30955|18-305: L26-R300 Leucine zipper pattern: L160-L181 MOTIFSG-protein coupled receptors signature: T110-I126 MOTIFS 52 7475185CD1322 S3 S129 S184 S287 N8 N38 N259 7-transmembrane receptor (rhodopsinfamily): G37- HMMER_PFAM S317 Y286 Transmembrane domains: D23-L51,L91-F119, T134- TMAP L162, V193-I221, T242-Y262, K268-L288 N-terminus iscytosolic. G-protein coupled receptor: BL00237: I203-Y214, BLIMPS_BLOCKSH231-M257, I278-K294, N86-P125 G-protein coupled receptors signature:F102-G148 PROFILESCAN Olfactory receptor signature: PR00245: M55-N76,BLIMPS_PRINTS F173-D187, F234-G249, V270-L281, S287-L301 OLFACTORYRECEPTOR PROTEIN RECEPTOR- BLAST_PRODOM LIKE G-PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD149621: T242-K304PD000921: L162-L241 G-PROTEIN COUPLED RECEPTORS: BLAS1UDOMODM00013|P37067|17-306: L20-R299 DM00013|S51356|18-307: L26-R299DM00013|S29709|11-299: T21-L301 DM00013|P23274|18-306: L30-L301G-protein coupled receptors signature: V106-I122 MOTIFS 53 7477369CD1314 S67 5229 S233 T8 N5 N65 7-transmembrane receptor (rhodopsin family):G41- HMMER_PFAM T78 T108 T224 Y287 T267 T288 Transmembrane domains:N19-I47, P58-T83, I101- TMAP A125, P138-L166, V190-Y218. G232-W260N-terminus is non-cytosolic. G-protein coupled receptor: BL00237:T279-K295, BLIMPS_BLOCKS K90-P129, R231-I257 G-protein coupled receptorssignature: F102-A147 PROFILESCAN Olfactory receptor signature: PR00245:M59-K80, BLIMPS_PRINTS F177-D191, L237-G252, L271-L282, T288-K302OLFACTORY RECEPTOR PROTEIN RECEPTOR- BLAST_PRODOM LIKE G-PROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY: PD149621: V246-R304G-PROTEIN COUPLED RECEPTORS: BLASLDOMO DM00013|S29710|15-301: F28-L301DM00013|P23266|17-306: L17-L301 DM00013|P23275|17-306: L17-L301DM00013|P23274|18-306: E22-M298 G-protein coupled receptors signature:T110-I126 MOTIFS 54 7495138CD1 315 S65 S76 S221 T264 N6 7-transmembranereceptor (rhodopsin family): G39- HMMER_PFAM T285 T304 Y284Transmembrane domains: Q22-L42, A49-A69. Q93- TMAP Y121, R136-P164,T189-Y215, A233-F253, P263- I283 N-terminus is non-cytosolic. G-proteincoupled receptor: BL00237: K88-P127, BLIMPS..BLOCKS E228:1254, T276R292G-protein coupled receptors signature: F100-G150 PROFILESCANRhodopsin-like GPCR superfamily signature BLIMPS_PRINTS PR00237:K266-R292, A24-I48, M57-K78, D102- I124, A24-V45, V196-L219, F140-P164Olfactory receptor signature: PR00245: M57-K78, BLIMPS_PRINTS F174-D188,L234-V249, M268-L279, T285-L299 RECEPTOR OLFACTORY PROTEIN RECEPTOR-BLAST_PRODOM LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD000921: L163-S239 OLFACTORY RECEPTOR PROTEIN RECEPTOR-BLAST_PRODOM LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD149621: T242-T304 G-PROTEIN COUPLED RECEPTORS: BLAST_DOMODM00013|S29710|15.301: S16-L298 DM00013|P23266|17-306: S16-L299DM00013|S29709|11-299: S16-G300 DM00013|457069|15-304: F15-G300G-protein coupled receptors signature: A108-I124 MOTIFS 55 7475830CD1324 S137 S188 S291 N265 7-transmembrane receptor (rhodopsin family):G41- HMMER_PFAM S301 T18 T78 Y290 T163T270 Transmembrane domains: L23-I51, P58-M82, 192- TMAP Y120, R139-T167, L198.Y2 18, Q232-Y252, 1-I266-N294 N terminus is non-cytosolic. G-protein coupled receptor: BL00237:N90-P129, BLIMPS_BLOCKS Q232-M258, I282-K298 Olfactory receptorsignature: PR00245: M59-K80, BLIMPS_PRINTS F177-D191, I238-G253,A274-L285, S291-L305 RECEPTOR OLFACTORY PROTEIN RECEPTOR- BLAST_PRODOMLIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MIJLTIGENE FAMILY:PD000921: L166-V246 OLFACTORY RECEPTOR PROTEIN RECEPTOR- BLAST_PRODOMLIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY:PD149621: V248-K307 G-PROTEIN COUPLED RECEPTORS: BLAST_DOMODM00013|S51356|18-307: I17-A300 DM00013|P37067|17-306: I17-K303DM00013|P23274|18-306: E22-L305 DM00013|S29709|11-299: T18-L305 567476161CD1 305 S66 S136 S229 N5 N41 N50 N64 Signal Peptide: M22-G41HMMER S290 T7 T77 T159 N154 7-transmembrane receptor (rhodopsin family):G40- HMMER_PFAM I221 Transmembrane domains: F16-L44, H55-W71, A134- TMAPK161, M198-R226, P261-Y289 N-terminus is non-cytosolic. G-proteincoupled receptor: BL00237: K89-P128, BLIMPS_BLOCKS V206-Y217, L234-L260,F281-K297 G-protein coupled receptors signature: F101-V146 PROFILESCANOlfactory receptor signature: PR00245: M58-K79, BLIMPS_PRINTS F176-E190,F237-G252, V273-L284, S290-L304 OLFACTORY RECEPTOR PROTEIN RECEPTOR-BLAST_PRODOM LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD149621: T245-L304 RECEPTOR OLFACTORY PROTEIN RECEPTOR-BLAST_PRODOM LIKE G-PROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY: PD000921: N166-L244 G-PROTEIN COUPLED RECEPTORS: BLAST_DOMODM00013|S51356|18-307: T17-L300 DM00013|P37067|17-306: T17-L303DM00013|S29709|11-299: T17-L304 DM00013|P23274|18-306: F27-L304G-protein coupled receptors signature: S109-I125 MOTIFS 57 7475235CD1313 S7 S110 S151 S167 N5 N44 7-transmembrane receptor (rhodopsinfamily): G43- HMMER_PFAM S231 T140 T164 Y293 Transmembrane domains:M19-I47, M61-F89, E103- TMAP P131, S136-T164, S192-I215, T241-V261,H268- M288 G-protein coupled receptor: BL00237: P92-P131, BLIMPS_BLOCKSK233-L259, P285-R301 G-protein coupled receptors signature: F104-S151PROFILESCAN Olfactory receptor signature PR00245: M61-T82, BLIMPS_PRINTSS179-D193, L239-L254, I11-L22 PUTATIVE G-PROTEIN COUPLED RECEPTORBLAST_PRODOM RAIC PD170483: I246-A306 G-PROTEIN COUPLED RECEPTORS:BLAST_DOMO DM00013|P23273|18-306: E23-C309 DM00013|G45774|18-309:P20-R301 DM00013|P23274|18-306: E23-C309 DM00013|D45774|24-314: G18-L308G-protein coupled receptors signature: L112-I128 MOTIFS 58 7476246CD1305 S3 S13 S283 T56 N135 N157 Transmembrane domains: R15-R35, L41-L61,G89- TMAP T121 S109, F120-S140, V169-M197, I217-F237, S242- Y262N-terminus is non-cytosolic. PHEROMONE RECEPTOR VN1 VN2 VN3 VN7BLAST_PRODOM VN5 VN4 VN6 PD009900: F30-Q292 59 7474899CD1 315 S71 S192S273 T3 N6 N46 N185 Signal Peptide: V22-A45 HMMER 7-transmembranereceptor (rhodopsin family): A45- HMMER_PFAM Y296 Transmembrane domains:S26-W54, L63-F91, Q104- TMAP Y127, S138-P164, N199-R227, M250-K270,V276- Y296 N terminus is non-cytosolic. G-protein coupled receptorBL00237: R94-P133, BLIMPS_BLOCKS A239-T265, P288-K304 G-protein coupledreceptors signature: Y106-L153 PROFILESCAN Olfactory receptor signaturePR00245: L63-K84, BLIMPS_PRINTS C181-D195, L242-T257, G297-L311G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|F45774|19-309: Q28-K312DM00013|P23266|17-306: R23-L311 DM00013|G45774|18-309: P25-L311DM00013|S29708|18-306: Q28-L311 Leucine zipper pattern: L72-L93 MOTIFS60 7478353CD1 324 S68 S157 S189 N6 N43 N66 Signal Peptide: M24-L40,M24-A41, M24-545 HMMER S292 T233 7 transmembrane receptor (rhodopsinfamily): W42- HMMER_PFAM Y291 Transmembrane domains: S19-I47 Q101-Y124N129- TMAP S157 V198-V226 R271-Y291 G-protein coupled receptorssignature BL00237: K91- BLIMPS_BLOCKS P130, E197-V223, I283-K299G-protein coupled receptors signature: F103-V147 PROFILESCAN Olfactoryreceptor signature PR00245: M60-K81, BLIMPS_PRINTS F178-D192, P239-0254,V275-V286, S292-M306 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: F169-L246 PD149621: T247-R308 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S29709|11-299: S19-M306 G-protein coupledreceptors signature: T111-I127 MOTIFS 61 7473910CD1 314 S69 S139 S190 N7N169 signal_cleavage: M1-G43 SPSCAN S234 S293 T80 7 transmembranereceptor (rhodopsin family): G43- HMMER_PFAM T206 T272 Y292Transmembrane domains: L25-I53 P60-S76 F97-F125 TMAP A137-A165 L186-T206M210-I230 G235-V263 N-terminus is non-cytosolic G-protein coupledreceptors signature BL00237: BLIMPS_BLOCKS N284-K300, K92-P131 G-proteincoupled receptors signature: F104-G149 PROFILESCAN Olfactory receptorsignature PR00245: M61-K82, BLIMPS_PRINTS F179-D193, F240-G255,A276-L287, S293-I307 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN M1JLTIGENEFAMILY PD000921: L168-L247 PD149621: T248-I307 6-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S51356|18-307: T20-A302 6-protein coupledreceptors signature: T112-I128 MOTIFS 62 7476047CD1 210 S130 S193 T8 T18Signal Peptide: M44-F68 HMMER T107 7 transrnernbrane receptor (rhodopsinfamily): L15- HMMER PFAM R40, P185-Y192 Transmembrane domains: L47-R70I97-V125 F138- TMAP R166 R170-I190 N-terminus is non-cytosolic G-proteincoupled receptors signature: F2-R51 PROFILESCAN Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: L4-I26, R40-L61, G99-I122,V137-V161, S174-R200 Olfactory receptor signature PR00245: F138-I153,BLIMPS_PRINTS S77-D91 PUTATIVE GPROTEIN COUPLED RECEPTOR BLAST_PRODOMRAIC PD170483: V145-L206 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P23273|18-306: M1-L207 G-protein coupled receptors signature:M10-I26 MOTIFS 63 7289994CD1 924 S129 S133 S184 N99 N210 N335 ZU5domain: T511-G613 HMMER_PFAM S224 S239 S377 N347 N476 N486 Death domain:Q830-Q910 HMMER_PFAM S467 S620 5724 N503 N858 N905 Immunoglobulindomain: E155-A215 HMMER_PFAM S752 S774 S794 N917 Thrombospondin type 1domain: S238-C287, E294- HMMER_PFAM S798 S827 S909 C341 T16 T84 T126Transmembrane domain: D350-R376 TMAP T192 T402 T509 N-terminus iscytosolic T610 Y211 TRANSMEMBRANE RECEPTOR UNC5 C BLAST_PRODOM ELEGANSUNC5H1 UNC5H2 HOMOLOG ROSTRAL CEREBELLAR MALFORMATION PD011882:W615-Q910 PD016327: D14-F143 PD152442: L340-N496 C. ELEGANS UNC5 NID:G25852 PD145050:N217- BLAST_PRODOM V371 64 7482840CD1 313 S7 S56 S110S151 N5 N44 7 transmembrane receptor (rhodopsin family): G43- HMMER_PFAMS231 T140 T164 Y293 Transmembrane domains: M19-I47 Y62-N90 E103- TMAPP131 S136-T164 S192-I215 T241-V261 H268-T288 N-terminus is non-cytosolicG-protein coupled receptors signature BL00237: P92- BLIMPS_BLOCKS P131,K233-L259, P285-R301 G-protein coupled receptors signature: F104-K153PROFILESCAN Olfactory receptor signature PR00245: M61-T82, BLIMPS_PRINTSS179-D193, L239-L254 PUTATIVE GPROTEIN COUPLED RECEPTOR BLAST_PRODOMRAIC PD170483: 1246-I313 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PDa00921: L168-I246 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P23273|18-306: E23-C309 G-protein coupled receptors signature:L112-I128 MOTIFS 65 55093631CD1 320 S62 S157 T145 N11 N275signal_cleavage: M1-H64 SPSCAN T185 7 transmembrane receptor (rhodopsinfamily): G49- HMMER_PFAM Y300 Transmembrane domains: P26-L54 F68-K88F93- TMAP H113 G155-I181 I202-I229 L246-H270 S277-M298 N-terminus isnon-cytosolic G-protein coupled receptors signature BL00237:BLIMPS_BLOCKS D240-5266, P292-R308, R98-P137 Olfactory receptorsignature PR00245: M67-K88, BLIMPS_PRINTS T185-D199, L246-T261,F284-L295 PUTATIVE GPROTEIN COUPLED RECEPTOR BLAST_PRODOM RAIC PD170483: V255-F315 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKEGPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921:L174-V253 G-PROTEIN COUPLED RECEPTORS BLAST_DOMO DM00013|G45774|18-309:P26-D309 66 7474992CD1 313 S70 S78 S140 S191 N8 N68 N92 signaLcleavage:M1-A39 SPSCAN S292 Y181 7 transmembrane receptor (rhodopsin family):G44- HMMER_PFAM Y291 Transmembrane domains: F20-M48 P61-W89 A98- TMAPF126 I197-I224 E235-Y262 N-terminus is non-cytosolic G-protein coupledreceptors signature BL00237: T283 BLIMPS_BLOCKS Q299, K93-P132,I210-Y221, K238-T264 G-protein coupled receptors signature: F105-G150PROFILESCAN Rhodopsin-like GPCR superfamily signature BLIMPS_PRINTSPR00237: L29-M53, M62-K83, F107-I129, S202- V225, A240-T264, K273-Q299Olfactory receptor signature PR00245: M62-K83, BLIMPS_PRINTS F180-D194,F241-G256, A275-L286, S292-L306 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOMRECEPTORLIKE GPROTEIN COUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENEFAMILY PD000921: L169-L248 PD149621: V250-K309 G-PROTEIN COUPLEDRECEPTORS BLAST_DOMO DM00013|S51356|18-307: R23-F305 G-protein coupledreceptors signature: T113-I129 MOTIFS 67 7476244CD1 310 S6 S49 S65 S85N4 N225 7 transmembrane receptor (rhodopsin family): G39- HMMER_PFAMS222 S227 T46 T91 S199, I211-Y285 T286 Transmembrane domains: R21-549R51-F71 M96- TMAP I124 Q136-L164 L197-I217 K231-P251 N-terminus isnon-cytosolic G-protein coupled receptors signature BL00237: K88BLIMPS_BLOCKS P127, K229-I255, T277-K293 G-protein coupled receptorssignature: F100-L145 PROFILESCAN Visual pigments (opsins) retinalbinding site: Y256- PROFILESCAN G310 Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: I24-K48, M57-R78, L102-I124, V138-I159, L197-L220, A234-R258, K267-K293 Olfactory receptor signaturePR00245: M57-R78, BLIMPS_PRINTS Y175-D189, L235-G250, V269-L280,T286-W300 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEINCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L164-I243PD149621: V244-L299 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|S29710|15:301: L15-W300 G-protein coupled receptors signature:M108-I124 MOTIFS 68 7487604CD1 318 S49 S67 S87 S297 N5 N65 N91 N155 7transmembrane receptor (rhodopsin family): 041- HMMER_PFAM S312 T232Y296 Transmembrane domains: I26-I46 I50-D70 S95-Y123 TMAP R131-G152N175-N195 A205-I225 T232-Y259 A275-P293 N-terminus is non-cytosolic .G-protein coupled receptors signature BL00237: R90- BLIMPS_BLOCKS P129,L207-Y218, T232-M258, T288-K304 G-protein coupled receptors signature:F102-V147 PROFILESCAN Visual pigments (opsins) retinal binding site:L267- PROFILESCAN Q318 Rhodopsin-like GPCR superfamily signatureBLIMPS_PRINTS PR00237: I26-I50, M59-S80, G104-I126, L199-L222,A237-K261, G278-K304 Olfactory receptor signature PR00245: M59-S80,BLIMPS_PRINTS F177-D191, F238-G253, V280-L291, S297-L311 RECEPTOROLFACIORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: F168-L245PD149621: T246-K314 G-PRQTEIN COUPLED RECEPTORS BLAST_DOMO L17-L311G-protein coupled receptors signature: T110-I126 MOTIFS 69 7483200CD1313 S137 S291 S304 N5 7 transmembrane receptor (rhodopsin family): G41-HMMER_PFAM T18 T49 T160 Y290 T270 Y299 Transmembrane domains: L23-V51F85-L113 L144- TMAP N172 M197-I225 E232-Y259 T270-M288 N-terminus iscytosolic G-protein coupled receptors signature BL00237: I282-BLIMPS_BLOCKS K298, N9G-P129, P148-I174 G-protein coupled receptorssignature: F103-I147 PROFILESCAN Olfactory receptor signature PR00245:M59-K80, BLIMPS_PRINTS F177-N191, F238-G253, A274-L285, S291-L305RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245PD149621:T246-S310 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM000131551356118-307: 117-R303 G.protein coupled receptors signature:S110-I126 MOTIFS 70 7476069CD1 224 T110 N5 signaLcleavage: M1-A24 SPSCANSignal Peptide: M1-A24 HMMER 7 transmembrane receptor (rhodopsinfamily): G43- HMMER_PFAM T139 Transmembrane domains: H27-P55 P60-W88D97- TMAP F125 Y134-P162 T194-Y220 N-terminus is cytosolic G-proteincoupled receptors signature: F104-L151 PROFILESCAN Rhodopsin-like GPCRsuperfamily signature BLIMPS_PRINTS PR00237: W28-H52, M61-T82,I106-I128, V142- I163, G201-L224 Olfactory receptor signature PR00245:C179-D193, BLIMPS_PRINTS M61-T82 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P23274|18-306: E23-L224 G-protein coupled receptors signature:V112-I128 MOTIFS 71 7472453CD1 314 S67 S137 S230 N5 N42 7 transmembranereceptor (rhodopsin family): G41- HMMER_PFAM S291 S310 T8 T78 Y290 T192Transmembrane domains: E22-I49 T57-S75 I92-A117 TMAP M136-L164 G203-H229G233-K261 V273-R293 N-terminus is cytosolic G-protein coupled receptorssignature BL00237: R90- BLIMPS_BLOCKS P129, 1282-R298 G-protein coupledreceptors signature: F102-V151 PROFILESCAN Olfactory receptor signaturePR00245: M59-K80, BLIMPS_PRINTS Y177-S191, F238-G253, 5274-L285,S291-L305 RECEPTOR OLFACTORY PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEINCOUPLED TRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD000921: L166-L245PD149621: T246-5310 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|551356|18-307: L17-L301 G-protein coupled receptors signature:S110-I126 MOTIFS 72 5492483CD1 320 S67 S137 S193 N5 signal_cleavage:M1-T40 SPSCAN S230 S264 S291 7 transmembrane receptor (rhodopsinfamily): G41- HMMER_PFAM T91 Y290 Transmembrane domains: I23-I43 L51-L71L95-Y123 TMAP I140-P167 S193-R220 S239-R261 A273-F288 N-terminus isnon-cytosolic G-protein coupled receptors family BL00237: K90-BLIMPS_BLOCKS P129, F1S-M44, T282-T298 G-protein coupled receptorssignature: Y102-C147 PROFILESCAN Rhodopsin-like GPCR superfamilysignature BLIMPS_PRINTS PR00237: L26-R50, M59-K80, F104-I126, I140-L161, V199-L222, K272-T298 Olfactory receptor signature PR00245:V274-L285, BLIMPS_PRINTS S291-L305, M59-K80, F177-D191, V238-A253OLFACTORY RECEPTOR PROTEIN BLAST_PRODOM RECEPTORLIKE GPROTEIN COUPLEDTRANSMEMBRANE GLYCOPROTEIN MULTIGENE FAMILY PD 149621: V247-G306PD000921: L166-I246 G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|P23266|17-306: L26-L305 G-protein coupled receptors signature:T110-I126 MOTIFS 73 7472079CD1 318 S74 N10 N49 N188 7 transmembranereceptor (rhodopsin family): A48- HMMER_PFAM N198 Y299 Transmembranedomains: S29-I56 L66-Y94 S98- TMAP V124 H135-L161 L201-I228 I253-K273I279-Y299 N-terminus is non-cytosolic G-protein coupled receptorssignature BL00237: R97- BLIMPS_BLOCKS P136, G239-V265, P291-K307G-protein coupled receptors signature: F109-V157 PROFILESCAN Olfactoryreceptor signature PR00245: L66-K87, C184-N198, L245-T260, G300-L314Melanocortin receptor family signature PR00534: BLIMPS_PRINTS I133-T144,L172-L189, L58-L70 BLIMPS_PRINTS G-PROTEIN COUPLED RECEPTORS BLAST_DOMODM00013|G45774|18-309: L34-L314

[0368] TABLE 4 Polynucleotide SEQ ID NO:/ Incyte ID/Sequence LengthSequence Fragments 74/7475222CB1/930 1-455, 1-930, 310-380, 491-53675/7476060CB1/1151 1-1151, 94-1009 76/7476084CB1/1551 1-1551, 381-1551,479-1420, 1076-1245 77/7476110CB1/1151 1-1151, 92-103378/7476774CB1/1251 1-1251, 501-1088 79/7477364CB1/1129 1-1129, 103-103580/7477694CB1/1301 1-1301, 550-1161 81/7477940CB1/1201 1-1201, 342-109782/7477944CB1/1123 1-1123, 202-1023 83/7480405CB1/2053 1-1112, 346-1112,349-1110, 349-1112, 351-1112, 352-1110, 352-1112, 356-1112, 401-2053,408-1112, 409-1112, 969-1898 84/7482486CB1/939 1-939, 162-365, 162-36885/7482535CB1/930 1-921, 1-930, 729-774 86/7482770CB1/1301 1-1301,347-541, 347-543, 350-541, 350-543, 353-543 87/7475695CB1/1201 1-1201,128-1105 88/7477365CB1/1201 1-1201, 479-1066 89/7479899CB1/1355 1-1355,194-807 90/7480412CB1/1501 1-1501, 273-356, 273-1319, 357-44091/7485460CB1/1301 1-1301, 126-1070, 281-484 92/7472173CB1/1401 1-1401,201-1401, 301-1401, 592-1328 93/7475690CB1/1116 1-1116, 92-103094/7476068CB1/1352 1-1352, 207-1163 95/7476163CB1/1101 1-1101, 98-104296/7476166CB1/1201 1-1201, 296-1096 97/7476686CB1/1301 1-1301, 677-112698/7477363CB1/1301 1-1301, 404-1138 99/7477368CB1/1152 1-304, 212-1060,834-1152 100/7480408CB1/1408 1-1408, 273-1196 101/7480409CB1/13011-1301, 221-1185 102/7482487CB1/1476 1-1476, 281-1376, 281-1476103/7485424CB1/1331 1-1331, 187-1131, 442-1131 104/7475196CB1/966 1-786,1-966 105/7475295CB1/1101 1-1101, 719-1021 106/7478361CB1/1351 1-1351,204-1139 107/7482534CB1/1301 1-1301, 125-1075 108/7490493CB1/1352 1-854,46-854, 57-854, 64-854, 79-854, 88-854, 94-854, 107-854, 122-854,420-1091, 875-1352 109/58001274CB1/1787 1-1182, 950-1510, 952-1317,952-1354, 952-1429, 952-1431, 952-1441, 952-1444, 952-1450, 952-1452,952-1454, 952-1456, 952-1460, 952-1510, 952-1787, 955-1510110/7476809CB1/1251 1-1251, 119-1063 111/7476048CB1/1401 1-1401,210-1193 112/7476679CB1/1162 1-1162, 636-1007 113/7486996CB1/11971-1197, 101-1197 114/7490489CB1/1701 1-401, 201-1701, 604-948115/7475304CB1/939 1-939 116/7475248CB1/973 1-947, 1-973, 11-937117/7475191CB1/1204 1-1204 118/7480413CB1/2011 1-2011, 889-1730,1001-2011 119/7476165CB1/1402 1-1402, 201-1402, 301-1402120/7478345CB1/2201 1-1201, 701-1701, 701-2201 121/7475245CB1/11931-1193 122/7485481CB1/1036 1-1036, 51-986, 54-986 123/7482835CB1/10961-1096, 51-1046 124/7475100CB1/1133 1-1133, 101-1039 125/7475185CB1/11981-1198, 188-1156 126/7477369CB1/1397 1-1397 127/7495138CB1/1051 1-1051128/7475830CB1/1236 1-1236 129/7476161CB1/1287 1-1287, 51-988, 51-1287130/7475235CB1/1276 1-1276 131/7476246CB1/1097 1-1097, 573-865132/7474899CB1/1323 1-423, 212-972, 232-638, 278-1323, 281-1323133/7478353CB1/1124 1-1124, 101-1024, 104-1024, 455-500, 603-861134/7473910CB1/1112 1-1112 135/7476047CB1/633 1-633 136/7289994CB1/29791-435, 169-433, 169-577, 169-683, 215-1844, 355-405, 355-551, 355-1108,434-577, 434-683, 578-683, 643-701, 681-754, 681-1199, 682-862,682-1030, 682-1844, 682-2937, 748-824, 863-989, 863-1030, 863-1108,863-1195, 1031-1128, 1031-1195, 1031-1375, 1196-1375, 1292-1627,1292-1885, 1381-1849, 1381-1885, 1382-1548, 1465-1841, 1572-1759,1572-1844, 1579-2110, 1760-1844, 1760-2013, 1842-2103, 1852-2013,1904-2735, 2014-2241, 2014-2391, 2242-2391, 2242-2556, 2392-2556,2392-2735, 2480-2640, 2482-2979, 2557-2735, 2557-2937, 2692-2720,2736-2937 137/7482840CB1/1191 1-1091, 1-1191, 201-1091, 204-1091138/55093631CB1/1385 1-819, 4-813, 352-1033, 696-1385139/7474992CB1/1203 1-1203, 101-1203, 201-1103, 204-1103140/7476244CB1/1300 1-1300, 303-701 141/7487604CB1/957 1-954, 1-957,352-957 142/7483200CB1/1300 1-1300 143/7476069CB1/1185 1-557, 1-638,1-785, 1-806, 2-822, 4-622, 7-822, 26-822, 41-1185, 81-821, 572-1185144/7472453CB1/1227 1-1227, 452-1045 145/5492483CB1/1498 1-1498146/7472079CB1/1218 1-1218, 224-1045

[0369] TABLE 5 Polynucleotide SEQ ID NO: Incyte Project ID:Representative Library 84 7482486CB1 GPCRDPV02 86 7482770CB1 GPCRDPV0291 7485460CB1 GPCRDNV39 131 7476246CB1 HEAPNOT01 136 7289994CB1BRAIFER06

[0370] TABLE 6 Library Vector Library Description BRAIFER06 PCDNA2.1This random primed library was constructed using RNA isolated from braintissue removed from a Caucasian male fetus who was stillborn with ahypoplastic left heart at 23 weeks' gestation. Serologies were negative.GPCRDNV39 PCR2- Library was constructed using pooled cDNA from differentdonors. cDNA was generated using mRNA isolated from the TOPOTAfollowing: aorta, cerebellum, lymph nodes, muscle, tonsil (lymphoidhyperplasia), bladder tumor (invasive grade 3 transitional cellcarcinoma.), diseased breast (proliferative fibrocystic changes withoutatypia characterized by epithelial ductal hyperplasia, testicle tumor(embryonal carcinoma), spleen, ovary, parathyroid, ileum, breast skin,sigmoid colon, penis tumor (fungating invasive grade 4 squamous cellcarcinoma), fetal lung,, breast, fetal small intestine, fetal liver,fetal pancreas, fetal lung, fetal skin, fetal penis, fetal bone, fetalribs, frontal brain tumor (grade 4 gemistocytic stomach, lymph nodeastrocytoma), ovary (stromal hyperthecosis), bladder, bladder tumor(invasive grade 3 transitional cell carcinoma), tumor (metastaticbasaloid squamous cell carcinoma), tonsil (reactive lymphoidhyperplasia), periosteum from the tibia, fetal brain, fetal spleen,uterus tumor, endometrial (grade 3 adenosquamous carcinoma), seminalvesicle, liver, aorta, adrenal gland, lymph node (metastatic grade 3squamous cell carcinoma), glossal muscle, esophagus, esophagus tumor(invasive grade 3 adenocarcinoma), ileum, pancreas, soft tissue tumorfrom the skull (grade 3 ependymoma), transverse colon, (benign familialpolyposis), rectum tumor (grade 3 colonic adenocarcinoma), rib tumor,(metastatic grade 3 osteosarcoma), lung, heart, placenta, thymus,stomach, spleen (splenomegaly with congestion), uterus, cervix (mildchronic cervicitis with focal squamous metaplasia), spleen tumor(malignant lymphoma, diffuse large cell type, B-cell phenotype withabundant reactive T-cells and marked granulomatous response), umbilicalcord blood mononuclear cells, upper lobe lung tumor, (grade 3 squamouscell carcinoma), endometrium (secretory phase), liver, liver tumor(metastatic grade 2 neuroendocrine carcinoma), colon, umbilical cordblood, Th1 cells, nonactivated, umbilical cord blood, Th2 cells,nonactivated, coronary artery endothelial cells (untreated), coronaryartery smooth muscle cells, (untreated), coronary artery smooth musclecells (treated with TNF & IL1 10 ng/mL each for 20 hours), bladder (mildchronic cystitis), epiglottis, breast skin, small intestine, fetalprostate stroma fibroblasts, prostate epithelial cells (PrEC cells),fetal adrenal glands, fetal liver, kidney transformed embryonal cellline (293-EBNA) (untreated), kidney transformed embryonal cell line(293-EBNA) (treated with 5Aza-2deoxycytidine for 72 hours), mammaryepithelial cells, (HMEC cells), peripheral blood monocytes (treated withIL-10 at time 0, 10 ng/ml, LPS was added at 1 hour at 5 ng/ml.Incubation 24 hours), peripheral blood monocytes (treated withanti-IL-10 at time 0, 10 ng/ml, LPS was added at 1 hour at 5 ng/ml.Incubation 24 hours), spinal cord, base of medulla (Huntington'schorea), thigh and arm muscle (ALS), breast skin fibroblast (untreated),breast skin fibroblast (treated with 9 CIS Retinoic Acid 1 μM for 20hours), breast skin fibroblast (treated with TNF-alpha & IL-1 beta, 10ng/ml each for 20 hours), fetal liver mast cells, hematopoietic (Mastcells prepared from human fetal liver hematopoietic progenitor cells(CD34+ stem cells) cultured in the presence of hIL-6 and hSCF for 18days), epithelial layer of colon, bronchial epithelial cells (treatedfor 20 hours with 20% smoke conditioned media), lymph node, pooledperipheral blood mononuclear cells (untreated), pooled brain segments:striatum, globus pallidus and posterior putamen (Alzheimer's Disease),pituitary gland, umbilical cord blood, CD34+ derived dendritic cells(treated with SCF, GM-CSF & TNF alpha, 13 days), umbilical cord blood,CD34+ derived dendritic cells (treated with SCF, GM-CSF & TNF alpha, 13days followed by PMA/Ionomycin for 5 hours), small intestine, rectum,bone marrow neuroblastoma cell line (SH-SY5Y cells, treated with6-Hydroxydopamine 100 uM for 8 hours), bone marrow, neuroblastoma cellline (SH-SY5Y cells, untreated), brain segments from one donor:amygdala, entorhinal cortex, globus pallidus, substantia innominata,striatum, dorsal caudate nucleus, dorsal putamen, ventral nucleusaccumbens, archaecortex (hippocampus anterior and posterior), thalamus,nucleus raphe magnus, periaqueductal gray, midbrain, substantia nigra,and dentate nucleus, pineal gland (Alzheimer's Disease), preadipocytes(untreated), preadipocytes (treated with a peroxisomeproliferator-activated receptor gamma agonist, 1 microM, 4 hours),pooled prostate (adenofibromatous hyperplasia), pooled kidney, pooledadipocytes (untreated), pooled adipocytes (treated with human insulin),pooled mesentaric and abdominal fat, pooled adrenal glands, pooledthyroid (normal and adenomatous hyperplasia), pooled spleen (normal andwith changes consistent with idiopathic thrombocytopenic purpura),pooled right and left breast, pooled lung, pooled nasal polyps, pooledfat, pooled synovium (normal and rhumatoid arthritis), pooled brain(meningioma, gemistocytic astrocytoma. and Alzheimer's disease), pooledfetal colon, pooled colon: ascending, descending (chronic ulcerativecolitis), and rectal tumor (adenocarcinoma), pooled esophagus, normaland tumor (invasive grade 3 adenocarcinoma), pooled breast skinfibroblast (one treated w/9 CIS Retinoic Acid and the other withTNF-alpha & IL-1 beta), pooled gallbladder (acute necrotizingcholecystitis with cholelithiasis (clinically hydrops), acutehemorrhagic cholecystitis with cholelithiasis, chronic cholecystitis andcholelithiasis), pooled fetal heart, (Patau's and fetal demise), pooledneurogenic tumor cell line, SK-N-MC, (neuroepitelioma, metastasis tosupra-orbital area, untreated) and neuron, NT-2 cell line, (treated withmouse leptin at 1 μg/ml and 9 cis retinoic acid at 3.3 μM for 6 days),pooled ovary (normal and polycystic ovarian disease), pooled prostate,(adenofibromatous hyperplasia), pooled seminal vesicle, pooled smallintestine, pooled fetal small intestine, pooled stomach and fetalstomach, prostate epithelial cells, pooled testis (normal and embryonalcarcinoma), pooled uterus, pooled uterus tumor (grade 3 adenosquamouscarcinoma and leiomyoma), pooled uterus, endometrium, and myometrium,(normal and adenomatous hyperplasia with squamous metaplasia and focalatypia), pooled brain: (temporal lobe meningioma, cerebellum andhippocampus (Alzheimer's Disease), and pooled skin GPCRDPV02 PCR2-Library was constructed using pooled cDNA from different donors. cDNAwas generated using mRNA isolated from the TOPOTA following: aorta,cerebellum, lymph nodes, muscle, tonsil (lymphoid hyperplasia), bladdertumor (invasive grade 3 transitional cell carcinoma), breast(proliferative fibrocystic changes without atypia characterized byepithilial ductal hyperplasia, testicle tumor (embryonal carcinoma),spleen, ovary, parathyroid, ileum, breast skin, sigmoid colon, penistumor (fungating invasive grade 4 squamous cell carcinoma), fetal lung,breast, fetal small intestine, fetal liver, fetal pancreas, fetal lung,fetal skin, fetal penis, fetal bone, fetal ribs, frontal brain tumor(grade 4 gemistocytic astrocytoma), ovary (stromal hyperthecosis),bladder, bladder tumor (invasive grade 3 transitional cell carcinoma),stomach, lymph node tumor (metastatic basaloid squamous cell carcinoma),tonsil (reactive lymphoid hyperplasia), periosteum from the tibia, fetalbrain, fetal spleen, uterus tumor, endometrial (grade 3 adenosquamouscarcinoma), seminal vesicle, liver, aorta, adrenal gland, lymph node(metastatic grade 3 squamous cell carcinoma), glossal muscle, esophagus,esophagus tumor (invasive grade 3 adenocarcinoma), ileum, pancreas, softtissue tumor from the skull (grade 3 ependymoma), transverse colon,(benign familial polyposis), rectum tumor (grade 3 colonicadenocarcinoma), rib tumor, (metastatic grade 3 osteosarcoma), lung,heart, placenta, thymus, stomach, spleen (splenomegaly with congestion),uterus, cervix (mild chronic cervicitis with focal squamous metaplasia),spleen tumor (malignant lymphoma, diffuse large cell type, B-cellphenotype with abundant reactive T-cells and marked granulomatousresponse), umbilical cord blood mononuclear cells, upper lobe lungtumor, (grade 3 squamous cell carcinoma), endometrium (secretory phase),liver, liver tumor blood, Th2 cells, (metastatic grade 2 neuroendocrinecarcinoma), colon, umbilical cord blood, Th1 cells, nonactivated,umbilical cord nonactivated, coronary artery endothelial cells(untreated), coronary artery, smooth muscle cells, (untreated), coronaryartery smooth muscle cells (treated with TNF & IL-1 10 ng/ml each for 20hrs), bladder (mild chronic cystitis), epiglottis, breast skin, smallintestine, fetal prostate stroma fibroblasts, prostate epithelial cells(PrEC cells), fetal adrenal glands, fetal liver, kidney transformedembryonal cell line (293-EBNA) (untreated), kidney transformed embryonalcell line (293-EBNA) (treated with 5Aza-2deoxycytidine for 72 hours),mammary epithelial cells, (HMEC cells), peripheral blood monocytes(treated with IL-10 at time 0, 10 ng/ml, LPS was added at 1 hour at 5ng/ml. Incubation 24 hrs), peripheral blood monocytes (treated withanti-IL-10 at time 0, 10 ng/ml, LPS was added at 1 hour at 5 ng/ml.Incubation 24 hrs), spinal cord, base of medulla (Huntington's chorea),thigh and arm muscle (ALS), breast skin fibroblast (untreated), breastskin fibroblast (treated with 9 CIS Retinoic Acid 1 μM for 20 hrs),breast skin fibroblast (treated with TNF-alpha & IL-1 beta, 10 ng/mleach for 20 hrs), fetal liver mast cells, hematopoietic (Mast cellsprepared from human fetal liver hematopoietic progenitor cells (CD34+stem cells) cultured in the presence of hIL-6 and hSCF for 18 days),epithelial layer of colon, bronchial epithelial cells (treated for 20hrs with 20% smoke conditioned media), lymph node, pooled peripheralblood mononuclear cells (untreated), pooled brain segments: striatum,globus pallidus and posterior putamen (Alzheimer's Disease), pituitarygland, umbilical cord blood, CD34+ derived dendritic cells (treated withSCF, GM-CSF & TNF alpha, 13 days), umbilical cord blood, CD34+ deriveddendritic cells (treated with SCF, GM-CSF & TNF alpha, 13 days followedby PMA/Ionomycin for 5 hours), small intestine, rectum, bone marrowneuroblastoma cell line (SH-SY5Y cells, treated with 6-Hydroxydopamine100 uM for 8 hours), bone marrow, neuroblastoma cell line (SH-SY5Ycells, untreated), brain segments from one donor: amygdala, entorhinalcortex, globus pallidus, substantia innominata, striatum, dorsal caudatenucleus, dorsal putamen, ventral nucleus accumbens, archaecortex(hippocampus anterior and posterior), thalamus, nucleus raphe magnus,periaqueductal gray, midbrain, substantia nigra, and dentate nucleus,pineal gland (Alzheimer's Disease), preadipocytes (untreated),preadipocytes (treated with a peroxisome proliferator-activated receptorgamma agonist, 1 microM, 4 hours), pooled prostate (Adenofibromatoushyperplasia), pooled kidney, pooled adipocytes (untreated), pooledadipocytes (treated with human insulin), pooled mesentaric and abdomenalfat, pooled adrenal glands, pooled thyroid (normal and adenomatoushyperplasia), pooled spleen (normal and with changes consistent withidiopathic thrombocytopenic purpura), pooled right and left breast,pooled lung, pooled nasal polyps, pooled fat, pooled synovium (normaland rhumatoid arthritis), pooled brain (meningioma, gemistocyticastrocytoma. and Alzheimer's disease), pooled fetal colon, pooled colon:ascending, descending (chronic ulcerative colitis), and rectal tumor(adenocarcinoma), pooled esophagus, normal and tumor (invasive grade 3adenocarcinoma), pooled breast skin fibroblast (one treated w/9 CISRetinoic Acid and the other with TNF-alpha & IL-1 beta), pooledgallbladder (acute necrotizing cholecystitis with cholelithiasis(clinically hydrops), acute hemorrhagic cholecystitis withcholelithiasis, chronic cholecystitis and cholelithiasis), pooled fetalheart, (Patau's and fetal demise), pooled neurogenic tumor cell line,SK-N-MC, (neuroepitelioma, metastasis to supra-orbital area, untreated)and neuron, NT-2 cell line, (treated with mouse leptin at 1 μg/ml and 9cis retinoic acid at 3.3 μM for 6 days), pooled ovary (normal andpolycystic ovarian disease), pooled prostate, (Adenofibromatoushyperplasia), pooled seminal vesicle, pooled small intestine, pooledfetal small intestine, pooled stomach and fetal stomach, prostateepithelial cells, pooled testis (normal and embryonal carcinoma), pooleduterus, pooled uterus tumor (grade 3 adenosquamous carcinoma andleiomyoma), pooled uterus, endometrium, and myometrium, (normal andadenomatous hyperplasia with squamous metaplasia and focal atypia),pooled brain: (temporal lobe meningioma, cerebellum and hippocampus(Alzheimer's Disease), and pooled skin. HEAPNOT01 pINCY Library wasconstructed using RNA isolated from coronary artery plaque tissue from apool of eight donors during coronary atherectomy.

[0371] TABLE 7 Parameter Program Description Reference ThresholdABIFACTURA A program that removes vector sequences and AppliedBiosystems, Foster City, CA. masks ambiguous bases in nucleic acidsequences. ABI/ A Fast Data Finder useful in comparing and AppliedBiosystems, Foster City, CA; Mismatch < PARACEL annotating amino acid ornucleic acid sequences. Paracel Inc., Pasadena, CA. 50% FDF ABI Aprogram that assembles nucleic acid sequences. Applied Biosystems,Foster City, CA. AutoAssembler BLAST A Basic Local Alignment Search Tooluseful in Altschul, S. F. et al. (1990) J. Mol. Biol. ESTs: sequencesimilarity search for amino acid and 215: 403-410; Altschul, S. F. etal. (1997) Probability nucleic acid sequences. BLAST includes fiveNucleic Acids Res. 25: 3389-3402. value = 1.0E−8 functions: blastp,blastn, blastx, tblastn, and tblastx. or less Full Length sequences:Probability value = 1.0E−10 or less FASTA A Pearson and Lipman algorithmthat searches for Pearson, W. R. and D. J. Lipman (1988) Proc. ESTs:fasta E similarity between a query sequence and a group of Natl. AcadSci. USA 85: 2444-2448; Pearson, value = sequences of the same type.FASTA comprises as W. R. (1990) Methods Enzymol. 183: 63-98; 1.06E−6least five functions: fasta, tfasta, fastx, tfastx, and and Smith, T. F.and M. S. Waterman (1981) Assembled ssearch. Adv. Appl. Math. 2:482-489. ESTs: fasta Identity = 95% or greater and Match length = 200bases or greater; fastx E value = 1.0E−8 or less Full Length sequences:fastx score = 100 or greater BLIMPS A BLocks IMProved Searcher thatmatches a Henikoff, S. and J. G. Henikoff (1991) Nucleic Probabilitysequence against those in BLOCKS, PRINTS, Acids Res. 19: 6565-6572;Henikoff, J. G. and value = 1.0E−3 DOMO, PRODOM, and PFAM databases tosearch S. Henikoff (1996) Methods Enzymol. or less for gene families,sequence homology, and structural 266: 88-105; and Attwood, T. K. et al.(1997) J. fingerprint regions. Chem. Inf. Comput. Sci. 37: 417-424.HMMER An algorithm for searching a query sequence against Krogh, A. etal. (1994) J. Mol. Biol. PEAM, INCY, hidden Markov model (HMM)-baseddatabases of 235: 1501-1531; Sonnhammer, E. L. L. et al. SMART, andprotein family consensus sequences, such as PFAM, (1988) Nucleic AcidsRes. 26: 320-322; TIGRFAM INCY, SMART, and TIGRFAM. Durbin, R. et al.(1998) Our World View, in a hits: Nutshell, Cambridge Univ. Press, pp.1-350. Probability value = 1.0E−3 or less Signal peptide hits: Score = 0or greater ProfileScan An algorithm that searches for structural andsequence Gribskov, M. et al. (1988) CABIOS 4: 61-66; Normalized motifsin protein sequences that match sequence patterns Gribskov, M. et al.(1989) Methods Enzymol. quality score ≧ defined in Prosite. 183:146-159; Bairoch, A. et al. (1997) GCG-specified Nucleic Acids Res. 25:217-221. “HIGH” value for that particular Prosite motif. Generally,score = 1.4-2.1. Phred A base-calling algorithm that examines automatedEwing, B. et al. (1998) Genome Res. sequencer traces with highsensitivity and probability. 8: 175-185; Ewing, B. and P. Green (1998)Genome Res. 8: 186-194. Phrap A Phils Revised Assembly Program includingSWAT and Smith, T. F. and M. S. Waterman (1981) Adv. Score = 120 orCrossMatch, programs based on efficient implementation Appl. Math. 2:482-489; Smith, T.F. and M.S. greater; of the Smith-Waterman algorithm,useful in searching Waterman (1981) J. Mol. Biol. 147: 195-197; Matchlength = sequence homology and assembling DNA sequences. and Green, P.,University of Washington, 56 or greater Seattle, WA. Consed A graphicaltool for viewing and editing Phrap assemblies. Gordon, D. et al. (1998)Genome Res. 8: 195-202. SPScan A weight matrix analysis program thatscans protein Nielson, H. et al. (1997) Protein Engineering Score = 3.5or sequences for the presence of secretory signal peptides. 10: 1-6;Claverie, J.M. and S. Audic (1997) greater CABIOS 12: 431-439. TMAP Aprogram that uses weight matrices to delineate Persson, B. and P. Argos(1994) J. Mol. Biol. transmembrane segments on protein sequences and237: 182-192; Persson, B. and P. Argos (1996) determine orientation.Protein Sci. 5: 363-371. TMHMMER A program that uses a hidden Markovmodel (HMM) to Sonnhammer, E. L. et al. (1998) Proc. Sixth Intl.delineate transmembrane segments on protein sequences Conf. onIntelligent Systems for Mol. Biol., and determine orientation. Glasgowet al., eds., The Am. Assoc. for Artificial Intelligence Press, MenloPark, CA, pp. 175-182. Motifs A program that searches amino acidsequences for patterns Bairoch, A. et al. (1997) Nucleic Acids thatmatched those defined in Prosite. Res. 25: 217-221; Wisconsin PackageProgram Manual, version 9, page M51-59, Genetics Computer Group,Madison, WI.

[0372]

1 146 1 309 PRT Homo sapiens misc_feature Incyte ID No 7475222CD1 1 MetAla Ser Thr Ser Asn Val Thr Glu Leu Ile Phe Thr Gly Leu 1 5 10 15 PheGln Asp Pro Ala Val Gln Ser Val Cys Phe Val Val Phe Leu 20 25 30 Pro ValTyr Leu Ala Thr Val Val Gly Asn Gly Leu Ile Val Leu 35 40 45 Thr Val SerIle Ser Lys Ser Leu Asp Ser Pro Met Tyr Phe Phe 50 55 60 Leu Ser Gly LeuSer Leu Val Glu Ile Ser Tyr Ser Ser Thr Ile 65 70 75 Ala Pro Lys Phe IleIle Asp Leu Leu Ala Lys Ile Lys Thr Ile 80 85 90 Ser Leu Glu Gly Cys LeuThr Gln Ile Phe Phe Phe His Phe Phe 95 100 105 Gly Val Ala Glu Ile LeuLeu Ile Val Val Met Ala Tyr Asp Cys 110 115 120 Tyr Val Ala Ile Cys LysPro Leu His Tyr Ile Tyr Ile Ile Ser 125 130 135 Arg Gln Leu Cys His LeuLeu Val Asp Gly Phe Arg Leu Gly Gly 140 145 150 Phe Cys His Ser Ile IleGln Ile Leu Val Ile Ile Gln Leu Pro 155 160 165 Phe Cys Gly Pro Asn ValIle Asp His Tyr Phe Cys Asp Leu Gln 170 175 180 Pro Leu Phe Lys Leu AlaCys Thr Asp Thr Phe Met Glu Gly Val 185 190 195 Ile Val Leu Ala Asn SerGly Leu Phe Ser Val Phe Ser Phe Leu 200 205 210 Ile Leu Val Ser Ser TyrIle Val Ile Leu Val Asn Leu Arg Asn 215 220 225 His Ser Ala Glu Gly ArgHis Lys Ala Leu Ser Thr Cys Ala Ser 230 235 240 His Ile Thr Val Val IleLeu Phe Phe Gly Pro Ala Ile Phe Leu 245 250 255 Tyr Met Arg Pro Ser SerThr Phe Thr Glu Asp Lys Leu Val Ala 260 265 270 Val Phe Tyr Thr Val IleThr Pro Met Leu Asn Pro Ile Ile Tyr 275 280 285 Thr Leu Arg Asn Ala GluVal Lys Ile Ala Ile Arg Arg Leu Trp 290 295 300 Ser Lys Lys Glu Asn ProGly Arg Glu 305 2 322 PRT Homo sapiens misc_feature Incyte ID No7476060CD1 2 Met Ser Pro Glu Asn Gln Ser Ser Val Ser Glu Phe Leu Leu Leu1 5 10 15 Gly Leu Pro Ile Arg Pro Glu Gln Gln Ala Val Phe Phe Ala Leu 2025 30 Phe Leu Gly Met Tyr Leu Thr Thr Val Leu Gly Asn Leu Leu Ile 35 4045 Met Leu Leu Ile Gln Leu Asp Ser His Leu His Thr Pro Met Tyr 50 55 60Phe Phe Leu Ser His Leu Ala Leu Thr Asp Ile Ser Phe Ser Ser 65 70 75 ValThr Val Pro Lys Met Leu Met Asn Met Gln Thr Gln His Leu 80 85 90 Ala ValPhe Tyr Lys Gly Cys Ile Ser Gln Thr Tyr Phe Phe Ile 95 100 105 Phe PheAla Asp Leu Asp Ser Phe Leu Ile Thr Ser Met Ala Tyr 110 115 120 Asp ArgTyr Val Ala Ile Cys His Pro Leu His Tyr Ala Thr Ile 125 130 135 Met ThrGln Ser Gln Cys Val Met Leu Val Ala Gly Ser Trp Val 140 145 150 Ile AlaCys Ala Cys Ala Leu Leu His Thr Leu Leu Leu Ala Gln 155 160 165 Leu SerPhe Cys Ala Asp His Ile Ile Pro His Tyr Phe Cys Asp 170 175 180 Leu GlyAla Leu Leu Lys Leu Ser Cys Ser Asp Thr Ser Leu Asn 185 190 195 Gln LeuAla Ile Phe Thr Ala Ala Leu Thr Ala Ile Met Leu Pro 200 205 210 Phe LeuCys Ile Leu Val Ser Tyr Gly His Ile Gly Val Thr Ile 215 220 225 Leu GlnIle Pro Ser Thr Lys Gly Ile Cys Lys Ala Leu Ser Thr 230 235 240 Cys GlySer His Leu Ser Val Val Thr Ile Tyr Tyr Arg Thr Ile 245 250 255 Ile GlyLeu Tyr Phe Leu Pro Pro Ser Ser Asn Thr Asn Asp Lys 260 265 270 Asn IleIle Ala Ser Val Ile Tyr Thr Ala Val Thr Pro Met Leu 275 280 285 Asn ProPhe Ile Tyr Ser Leu Arg Asn Lys Asp Ile Lys Gly Ala 290 295 300 Leu ArgLys Leu Leu Ser Arg Ser Gly Ala Val Ala His Ala Cys 305 310 315 Asn LeuSer Thr Leu Gly Gly 320 3 313 PRT Homo sapiens misc_feature Incyte ID No7476084CD1 3 Met Ala Asn Leu Ser Gln Pro Ser Glu Phe Val Leu Leu Gly Phe1 5 10 15 Ser Ser Phe Gly Glu Leu Gln Ala Leu Leu Tyr Gly Pro Phe Leu 2025 30 Met Leu Tyr Leu Leu Ala Phe Met Gly Asn Thr Ile Ile Ile Val 35 4045 Met Val Ile Ala Asp Thr His Leu His Thr Pro Met Tyr Phe Phe 50 55 60Leu Gly Asn Phe Ser Leu Leu Glu Ile Leu Val Thr Met Thr Ala 65 70 75 ValPro Arg Met Leu Ser Asp Leu Leu Val Pro His Lys Val Ile 80 85 90 Thr PheThr Gly Cys Met Val Gln Phe Tyr Phe His Phe Ser Leu 95 100 105 Gly SerThr Ser Phe Leu Ile Leu Thr Asp Met Ala Leu Asp Arg 110 115 120 Phe ValAla Ile Cys His Pro Leu Arg Tyr Gly Thr Leu Met Ser 125 130 135 Arg AlaMet Cys Val Gln Leu Ala Gly Ala Ala Trp Ala Ala Pro 140 145 150 Phe LeuAla Met Val Pro Thr Val Leu Ser Arg Ala His Leu Asp 155 160 165 Tyr CysHis Gly Asp Val Ile Asn His Phe Phe Cys Asp Asn Glu 170 175 180 Pro LeuLeu Gln Leu Ser Cys Ser Asp Thr Arg Leu Leu Glu Phe 185 190 195 Trp AspPhe Leu Met Ala Leu Thr Phe Val Leu Ser Ser Phe Leu 200 205 210 Val ThrLeu Ile Ser Tyr Gly Tyr Ile Val Thr Thr Val Leu Arg 215 220 225 Ile ProSer Ala Ser Ser Cys Gln Lys Ala Phe Ser Thr Cys Gly 230 235 240 Ser HisLeu Thr Leu Val Phe Ile Gly Tyr Ser Ser Thr Ile Phe 245 250 255 Leu TyrVal Arg Pro Gly Lys Ala His Ser Val Gln Val Arg Lys 260 265 270 Val ValAla Leu Val Thr Ser Val Leu Thr Pro Phe Leu Asn Pro 275 280 285 Phe IleLeu Thr Phe Cys Asn Gln Thr Val Lys Thr Val Leu Gln 290 295 300 Gly GlnMet Gln Arg Leu Lys Gly Leu Cys Lys Ala Gln 305 310 4 313 PRT Homosapiens misc_feature Incyte ID No 7476110CD1 4 Met Glu Pro Arg Asn GlnThr Ser Ala Ser Gln Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser Glu Lys ProGlu Gln Glu Thr Leu Leu Phe Ser Leu 20 25 30 Phe Phe Cys Met Tyr Leu ValMet Val Val Gly Asn Leu Leu Ile 35 40 45 Ile Leu Ala Ile Ser Ile Asp SerHis Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ala Asn Leu Ser Leu ValAsp Phe Cys Leu Ala Thr 65 70 75 Asn Thr Ile Pro Lys Met Leu Val Ser LeuGln Thr Gly Ser Lys 80 85 90 Ala Ile Ser Tyr Pro Cys Cys Leu Ile Gln MetTyr Phe Phe His 95 100 105 Phe Phe Gly Ile Val Asp Ser Val Ile Ile AlaMet Met Ala Tyr 110 115 120 Asp Arg Phe Val Ala Ile Cys His Pro Leu HisTyr Ala Lys Ile 125 130 135 Met Ser Leu Arg Leu Cys Arg Leu Leu Val GlyAla Leu Trp Ala 140 145 150 Phe Ser Cys Phe Ile Ser Leu Thr His Ile LeuLeu Met Ala Arg 155 160 165 Leu Val Phe Cys Gly Ser His Glu Val Pro HisTyr Phe Cys Asp 170 175 180 Leu Thr Pro Ile Leu Arg Leu Ser Cys Thr AspThr Ser Val Asn 185 190 195 Arg Ile Phe Ile Leu Ile Val Ala Gly Met ValIle Ala Thr Pro 200 205 210 Phe Val Cys Ile Leu Ala Ser Tyr Ala Arg IleLeu Val Ala Ile 215 220 225 Met Lys Val Pro Ser Ala Gly Gly Arg Lys LysAla Phe Ser Thr 230 235 240 Cys Ser Ser His Leu Ser Val Val Ala Leu PheTyr Gly Thr Thr 245 250 255 Ile Gly Val Tyr Leu Cys Pro Ser Ser Val LeuThr Thr Val Lys 260 265 270 Glu Lys Ala Ser Ala Val Met Tyr Thr Ala ValThr Pro Met Leu 275 280 285 Asn Pro Phe Ile Tyr Ser Leu Arg Asn Arg AspLeu Lys Gly Ala 290 295 300 Leu Arg Lys Leu Val Asn Arg Lys Ile Thr SerSer Ser 305 310 5 330 PRT Homo sapiens misc_feature Incyte ID No7476774CD1 5 Met Phe Phe Ile Ile His Ser Leu Val Thr Ser Val Phe Leu Thr1 5 10 15 Ala Leu Gly Pro Gln Asn Arg Thr Met His Phe Val Thr Glu Phe 2025 30 Val Leu Leu Gly Phe His Gly Gln Arg Glu Met Gln Ser Cys Phe 35 4045 Phe Ser Phe Ile Leu Val Leu Tyr Leu Leu Thr Leu Leu Gly Asn 50 55 60Gly Ala Ile Val Cys Ala Val Lys Leu Asp Arg Arg Leu His Thr 65 70 75 ProMet Tyr Ile Leu Leu Gly Asn Phe Ala Phe Leu Glu Ile Trp 80 85 90 Tyr IleSer Ser Thr Val Pro Asn Met Leu Val Asn Ile Leu Ser 95 100 105 Glu IleLys Thr Ile Ser Phe Ser Gly Cys Phe Leu Gln Phe Tyr 110 115 120 Phe PhePhe Ser Leu Gly Thr Thr Glu Cys Phe Phe Leu Ser Val 125 130 135 Met AlaTyr Asp Arg Tyr Leu Ala Ile Cys Arg Pro Leu His Tyr 140 145 150 Pro SerIle Met Thr Gly Lys Phe Cys Ile Ile Leu Val Cys Val 155 160 165 Cys TrpVal Gly Gly Phe Leu Cys Tyr Pro Val Pro Ile Val Leu 170 175 180 Ile SerGln Leu Pro Phe Cys Gly Pro Asn Ile Ile Asp His Leu 185 190 195 Val CysAsp Pro Gly Pro Leu Phe Ala Leu Ala Cys Ile Ser Ala 200 205 210 Pro SerThr Glu Leu Ile Cys Tyr Thr Phe Asn Ser Met Ile Ile 215 220 225 Phe GlyPro Phe Leu Ser Ile Leu Gly Ser Tyr Thr Leu Val Ile 230 235 240 Arg AlaVal Leu Cys Ile Pro Ser Gly Ala Gly Arg Thr Lys Ala 245 250 255 Phe SerThr Cys Gly Ser His Leu Met Val Val Ser Leu Phe Tyr 260 265 270 Gly ThrLeu Met Val Met Tyr Val Ser Pro Thr Ser Gly Asn Pro 275 280 285 Ala GlyMet Gln Lys Ile Ile Thr Leu Val Tyr Thr Ala Met Thr 290 295 300 Pro PheLeu Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Met 305 310 315 Lys AspAla Leu Lys Arg Val Leu Gly Leu Thr Val Ser Gln Asn 320 325 330 6 310PRT Homo sapiens misc_feature Incyte ID No 7477364CD1 6 Met Ala Gly AsnAsn Phe Thr Glu Val Thr Val Phe Ile Leu Ser 1 5 10 15 Gly Phe Ala AsnHis Pro Glu Leu Gln Val Ser Leu Phe Leu Met 20 25 30 Phe Leu Phe Ile TyrLeu Phe Thr Val Leu Gly Asn Leu Gly Leu 35 40 45 Ile Thr Leu Ile Arg MetAsp Ser Gln Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser Asn Leu AlaPhe Ile Asp Ile Phe Tyr Ser Ser 65 70 75 Thr Val Thr Pro Lys Ala Leu ValAsn Phe Gln Ser Asn Arg Arg 80 85 90 Ser Ile Ser Phe Val Gly Cys Phe ValGln Met Tyr Phe Phe Val 95 100 105 Gly Leu Val Cys Cys Glu Cys Phe LeuLeu Gly Ser Met Ala Tyr 110 115 120 Asn Arg Tyr Ile Ala Ile Cys Asn ProLeu Leu Tyr Ser Val Val 125 130 135 Met Ser Gln Lys Val Ser Asn Trp LeuGly Val Met Pro Tyr Val 140 145 150 Ile Gly Phe Thr Ser Ser Leu Ile SerVal Trp Val Ile Ser Ser 155 160 165 Leu Ala Phe Cys Asp Ser Ser Ile AsnHis Phe Phe Cys Asp Thr 170 175 180 Thr Ala Leu Leu Ala Leu Ser Cys ValAsp Thr Phe Gly Thr Glu 185 190 195 Met Val Ser Phe Val Leu Ala Gly PheThr Leu Leu Ser Ser Leu 200 205 210 Leu Ile Ile Thr Val Thr Tyr Ile IleIle Ile Ser Ala Ile Leu 215 220 225 Arg Ile Gln Ser Ala Ala Gly Arg GlnLys Ala Phe Ser Thr Cys 230 235 240 Ala Ser His Leu Met Ala Val Thr IlePhe Tyr Gly Ser Leu Ile 245 250 255 Phe Thr Tyr Leu Gln Pro Asp Asn ThrSer Ser Leu Thr Gln Ala 260 265 270 Gln Val Ala Ser Val Phe Tyr Thr IleVal Ile Pro Met Leu Asn 275 280 285 Pro Leu Ile Tyr Ser Leu Arg Asn LysAsp Val Lys Asn Ala Leu 290 295 300 Leu Arg Val Ile His Arg Lys Leu PhePro 305 310 7 320 PRT Homo sapiens misc_feature Incyte ID No 7477694CD17 Met Glu Arg Thr Asn Asp Ser Thr Ser Thr Glu Phe Phe Leu Val 1 5 10 15Gly Leu Ser Ala His Pro Lys Leu Gln Thr Val Phe Phe Val Leu 20 25 30 IleLeu Trp Met Tyr Leu Met Ile Leu Leu Gly Asn Gly Val Leu 35 40 45 Ile SerVal Ile Ile Phe Asp Ser His Leu His Thr Pro Met Tyr 50 55 60 Phe Phe LeuCys Asn Leu Ser Phe Leu Asp Val Cys Tyr Thr Ser 65 70 75 Ser Ser Val ProLeu Ile Leu Ala Ser Phe Leu Ala Val Lys Lys 80 85 90 Lys Val Ser Phe SerGly Cys Met Val Gln Met Phe Ile Ser Phe 95 100 105 Ala Met Gly Ala ThrGlu Cys Met Ile Leu Gly Thr Met Ala Leu 110 115 120 Asp Arg Tyr Val AlaIle Cys Tyr Pro Leu Arg Tyr Pro Val Ile 125 130 135 Met Ser Lys Gly AlaTyr Val Ala Met Ala Ala Gly Ser Trp Val 140 145 150 Thr Gly Leu Val AspSer Val Val Gln Thr Ala Phe Ala Met Gln 155 160 165 Leu Pro Phe Cys AlaAsn Asn Val Ile Lys His Phe Val Cys Glu 170 175 180 Ile Leu Ala Ile LeuLys Leu Ala Cys Ala Asp Ile Ser Ile Asn 185 190 195 Val Ile Ser Met ThrGly Ser Asn Leu Ile Val Leu Val Ile Pro 200 205 210 Leu Leu Val Ile SerIle Ser Tyr Ile Phe Ile Val Ala Thr Ile 215 220 225 Leu Arg Ile Pro SerThr Glu Gly Lys His Lys Ala Phe Ser Thr 230 235 240 Cys Ser Ala His LeuThr Val Val Ile Ile Phe Tyr Gly Thr Ile 245 250 255 Phe Phe Met Tyr AlaLys Pro Glu Ser Lys Ala Ser Val Asp Ser 260 265 270 Gly Asn Glu Asp IleIle Glu Ala Leu Ile Ser Leu Phe Tyr Gly 275 280 285 Val Met Thr Pro MetLeu Asn Pro Leu Ile Tyr Ser Leu Arg Asn 290 295 300 Lys Asp Val Lys AlaAla Val Lys Asn Ile Leu Cys Arg Lys Asn 305 310 315 Phe Ser Asp Gly Lys320 8 310 PRT Homo sapiens misc_feature Incyte ID No 7477940CD1 8 MetAsp Pro Gln Asn Tyr Ser Leu Val Ser Glu Phe Val Leu His 1 5 10 15 GlyLeu Cys Thr Ser Arg His Leu Gln Asn Phe Phe Phe Ile Phe 20 25 30 Phe PheGly Val Tyr Val Ala Ile Met Leu Gly Asn Leu Leu Ile 35 40 45 Leu Val ThrVal Ile Ser Asp Pro Cys Leu His Ser Ser Pro Met 50 55 60 Tyr Phe Leu LeuGly Asn Leu Ala Phe Leu Asp Met Trp Leu Ala 65 70 75 Ser Phe Ala Thr ProLys Met Ile Arg Asp Phe Leu Ser Asp Gln 80 85 90 Lys Leu Ile Ser Phe GlyGly Cys Met Ala Gln Ile Phe Phe Leu 95 100 105 His Phe Thr Gly Gly AlaGlu Met Val Leu Leu Val Ser Met Ala 110 115 120 Tyr Asp Arg Tyr Val AlaIle Cys Lys Pro Leu His Tyr Met Thr 125 130 135 Leu Met Ser Trp Gln ThrCys Ile Arg Leu Val Leu Ala Ser Trp 140 145 150 Val Val Gly Phe Val HisSer Ile Ser Gln Val Ala Phe Thr Val 155 160 165 Asn Leu Pro Tyr Cys GlyPro Asn Glu Val Asp Ser Phe Phe Cys 170 175 180 Asp Leu Pro Leu Val IleLys Leu Ala Cys Met Asp Thr Tyr Val 185 190 195 Leu Gly Ile Ile Met IleSer Asp Ser Gly Leu Leu Ser Leu Ser 200 205 210 Cys Phe Leu Leu Leu LeuIle Ser Tyr Thr Val Ile Leu Leu Ala 215 220 225 Ile Arg Gln Arg Ala AlaGly Ser Thr Ser Lys Ala Leu Ser Thr 230 235 240 Cys Ser Ala His Ile MetVal Val Thr Leu Phe Phe Gly Pro Cys 245 250 255 Ile Phe Val Tyr Val ArgPro Phe Ser Arg Phe Ser Val Asp Lys 260 265 270 Leu Leu Ser Val Phe TyrThr Ile Phe Thr Pro Leu Leu Asn Pro 275 280 285 Ile Ile Tyr Thr Leu ArgAsn Glu Glu Met Lys Ala Ala Met Lys 290 295 300 Lys Leu Gln Asn Arg ArgVal Thr Phe Gln 305 310 9 309 PRT Homo sapiens misc_feature Incyte ID No7477944CD1 9 Met Ala Asn Arg Asn Asn Val Thr Glu Phe Ile Leu Leu Gly Leu1 5 10 15 Thr Glu Asn Pro Lys Met Gln Lys Ile Ile Phe Val Val Phe Ser 2025 30 Val Ile Tyr Ile Asn Ala Met Ile Gly Asn Val Leu Ile Val Val 35 4045 Thr Ile Thr Ala Ser Pro Ser Leu Arg Ser Pro Met Tyr Phe Phe 50 55 60Leu Ala Tyr Leu Ser Phe Ile Asp Ala Cys Tyr Ser Ser Val Asn 65 70 75 ThrPro Lys Leu Ile Thr Asp Ser Leu Tyr Glu Asn Lys Thr Ile 80 85 90 Leu PheAsn Gly Cys Met Thr Gln Val Phe Gly Glu His Phe Phe 95 100 105 Arg GlyVal Glu Val Ile Leu Leu Thr Val Met Ala Tyr Asp His 110 115 120 Tyr ValAla Ile Cys Lys Pro Leu His Tyr Thr Thr Ile Met Lys 125 130 135 Gln HisVal Cys Ser Leu Leu Val Gly Val Ser Trp Val Gly Gly 140 145 150 Phe LeuHis Ala Thr Ile Gln Ile Leu Phe Ile Cys Gln Leu Pro 155 160 165 Phe CysGly Pro Asn Val Ile Asp His Phe Met Cys Asp Leu Tyr 170 175 180 Thr LeuIle Asn Leu Ala Cys Thr Asn Thr His Thr Leu Gly Leu 185 190 195 Phe IleAla Ala Asn Ser Gly Phe Ile Cys Leu Leu Asn Cys Leu 200 205 210 Leu LeuLeu Val Ser Cys Val Val Ile Leu Tyr Ser Leu Lys Thr 215 220 225 His SerLeu Glu Ala Arg His Glu Ala Leu Ser Thr Cys Val Ser 230 235 240 His IleThr Val Val Ile Leu Ser Phe Ile Pro Cys Ile Phe Val 245 250 255 Tyr MetArg Pro Pro Ala Thr Leu Pro Ile Asp Lys Ala Val Ala 260 265 270 Val PheTyr Thr Met Ile Thr Ser Met Leu Asn Pro Leu Ile Tyr 275 280 285 Thr LeuArg Asn Ala Gln Met Lys Asn Ala Ile Arg Lys Leu Cys 290 295 300 Ser ArgLys Ala Ile Ser Ser Val Lys 305 10 315 PRT Homo sapiens misc_featureIncyte ID No 7480405CD1 10 Met Ala Asn Ile Thr Arg Met Ala Asn His ThrGly Lys Leu Asp 1 5 10 15 Phe Ile Leu Met Gly Leu Phe Arg Arg Ser LysHis Pro Ala Leu 20 25 30 Leu Ser Val Val Ile Phe Val Val Phe Leu Lys AlaLeu Ser Gly 35 40 45 Asn Ala Val Leu Ile Leu Leu Ile His Cys Asp Ala HisLeu His 50 55 60 Ser Pro Met Tyr Phe Phe Ile Ser Gln Leu Ser Leu Met AspMet 65 70 75 Ala Tyr Ile Ser Val Thr Val Pro Lys Met Leu Leu Asp Gln Val80 85 90 Met Gly Val Asn Lys Val Ser Ala Pro Glu Cys Gly Met Gln Met 95100 105 Phe Leu Tyr Leu Thr Leu Ala Gly Ser Glu Phe Phe Leu Leu Ala 110115 120 Thr Met Ala Tyr Asp Arg Tyr Val Ala Ile Cys His Pro Leu Arg 125130 135 Tyr Pro Val Leu Met Asn His Arg Val Cys Leu Phe Leu Ala Ser 140145 150 Gly Cys Trp Phe Leu Gly Ser Val Asp Gly Phe Met Leu Thr Pro 155160 165 Ile Thr Met Ser Phe Pro Phe Cys Arg Ser Trp Glu Ile His His 170175 180 Phe Phe Cys Glu Val Pro Ala Val Thr Ile Leu Ser Cys Ser Asp 185190 195 Thr Ser Leu Tyr Glu Thr Leu Met Tyr Leu Cys Cys Val Leu Met 200205 210 Leu Leu Ile Pro Val Thr Ile Ile Ser Ser Ser Tyr Leu Leu Ile 215220 225 Leu Leu Thr Val His Arg Met Asn Ser Ala Glu Gly Arg Lys Lys 230235 240 Ala Phe Ala Thr Cys Ser Ser His Leu Thr Val Val Ile Leu Phe 245250 255 Tyr Gly Ala Ala Val Tyr Thr Tyr Met Leu Pro Ser Ser Tyr His 260265 270 Thr Pro Glu Lys Asp Met Met Val Ser Val Phe Tyr Thr Ile Leu 275280 285 Thr Pro Val Leu Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp 290295 300 Val Met Gly Ala Leu Lys Lys Met Leu Thr Val Arg Phe Val Leu 305310 315 11 312 PRT Homo sapiens misc_feature Incyte ID No 7482486CD1 11Met Arg Leu Ala Asn Gln Thr Leu Gly Gly Asp Phe Phe Leu Leu 1 5 10 15Gly Ile Phe Ser Gln Ile Ser His Pro Gly Arg Leu Cys Leu Leu 20 25 30 IlePhe Ser Ile Phe Leu Met Ala Val Ser Trp Asn Ile Thr Leu 35 40 45 Ile LeuLeu Ile His Ile Asp Ser Ser Leu His Thr Pro Met Tyr 50 55 60 Phe Phe IleAsn Gln Leu Ser Leu Ile Asp Leu Thr Tyr Ile Ser 65 70 75 Val Thr Val ProLys Met Leu Val Asn Gln Leu Ala Lys Asp Lys 80 85 90 Thr Ile Ser Val LeuGly Cys Gly Thr Gln Met Tyr Phe Tyr Leu 95 100 105 Gln Leu Gly Gly AlaGlu Cys Cys Leu Leu Ala Ala Met Ala Tyr 110 115 120 Asp Arg Tyr Val AlaIle Cys His Pro Leu Arg Tyr Ser Val Leu 125 130 135 Met Ser His Arg ValCys Leu Leu Leu Ala Ser Gly Cys Trp Phe 140 145 150 Val Gly Ser Val AspGly Phe Met Leu Thr Pro Ile Ala Met Ser 155 160 165 Phe Pro Phe Cys ArgSer His Glu Ile Gln His Phe Phe Cys Glu 170 175 180 Val Pro Ala Val LeuLys Leu Ser Cys Ser Asp Thr Ser Leu Tyr 185 190 195 Lys Ile Phe Met TyrLeu Cys Cys Val Ile Met Leu Leu Ile Pro 200 205 210 Val Thr Val Ile SerVal Ser Tyr Tyr Tyr Ile Ile Leu Thr Ile 215 220 225 His Lys Met Asn SerVal Glu Gly Arg Lys Lys Ala Phe Thr Thr 230 235 240 Cys Ser Ser His IleThr Val Val Ser Leu Phe Tyr Gly Ala Ala 245 250 255 Ile Tyr Asn Tyr MetLeu Pro Ser Ser Tyr Gln Thr Pro Glu Lys 260 265 270 Asp Met Met Ser SerPhe Phe Tyr Thr Ile Leu Thr Pro Val Leu 275 280 285 Asn Pro Ile Ile TyrSer Phe Arg Asn Lys Asp Val Thr Arg Ala 290 295 300 Leu Lys Lys Met LeuSer Val Gln Lys Pro Pro Tyr 305 310 12 309 PRT Homo sapiens misc_featureIncyte ID No 7482535CD1 12 Met Thr Leu Gly Asn Ser Thr Glu Val Thr GluPhe Tyr Leu Leu 1 5 10 15 Gly Phe Gly Ala Gln His Glu Phe Trp Cys IleLeu Phe Ile Val 20 25 30 Phe Leu Leu Ile Tyr Val Thr Ser Ile Met Gly AsnSer Gly Ile 35 40 45 Ile Leu Leu Ile Asn Thr Asp Ser Arg Phe Gln Thr LeuThr Tyr 50 55 60 Phe Phe Leu Gln His Leu Ala Phe Val Asp Ile Cys Tyr ThrSer 65 70 75 Ala Ile Thr Pro Lys Met Leu Gln Ser Phe Thr Glu Glu Lys Asn80 85 90 Leu Ile Leu Phe Gln Gly Cys Val Ile Gln Phe Leu Val Tyr Ala 95100 105 Thr Phe Ala Thr Ser Asp Cys Tyr Leu Leu Ala Met Met Ala Val 110115 120 Asp Pro Tyr Val Ala Ile Cys Lys Pro Leu His Tyr Thr Val Ile 125130 135 Met Ser Arg Thr Val Cys Ile Arg Leu Val Ala Gly Ser Tyr Ile 140145 150 Met Gly Ser Ile Asn Ala Ser Val Gln Thr Gly Phe Thr Cys Ser 155160 165 Leu Ser Phe Cys Lys Ser Asn Ser Ile Asn His Phe Phe Cys Asp 170175 180 Val Pro Pro Ile Leu Ala Leu Ser Cys Ser Asn Val Asp Ile Asn 185190 195 Ile Met Leu Leu Val Val Phe Val Gly Ser Asn Leu Ile Phe Thr 200205 210 Gly Leu Val Val Ile Phe Ser Tyr Ile Tyr Ile Met Ala Thr Ile 215220 225 Leu Lys Met Ser Ser Ser Ala Gly Arg Lys Lys Ser Phe Ser Thr 230235 240 Cys Ala Ser His Leu Thr Ala Val Thr Ile Phe Tyr Gly Thr Leu 245250 255 Ser Tyr Met Tyr Leu Gln Ser His Ser Asn Asn Ser Gln Glu Asn 260265 270 Met Lys Val Ala Phe Ile Phe Tyr Gly Thr Val Ile Pro Met Leu 275280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Glu Val Lys Glu Ala 290295 300 Leu Lys Val Ile Gly Lys Lys Leu Phe 305 13 312 PRT Homo sapiensmisc_feature Incyte ID No 7482770CD1 13 Met Glu Ala Gly Asn Gln Thr GlyPhe Leu Glu Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser Glu Asp Pro Glu LeuGln Pro Phe Ile Phe Gly Leu 20 25 30 Phe Leu Ser Met Tyr Leu Val Thr ValLeu Gly Asn Leu Leu Ile 35 40 45 Ile Leu Ala Ile Ser Ser Asp Ser His LeuHis Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser Asn Leu Ser Trp Val Asp IleCys Phe Ser Thr 65 70 75 Cys Ile Val Pro Lys Met Leu Val Asn Ile Gln ThrGlu Asn Lys 80 85 90 Ala Ile Ser Tyr Met Asp Cys Leu Thr Gln Val Tyr PheSer Met 95 100 105 Phe Phe Pro Ile Leu Asp Thr Leu Leu Leu Thr Val MetAla Tyr 110 115 120 Asp Arg Phe Val Ala Val Cys His Pro Leu His Tyr MetIle Ile 125 130 135 Met Asn Pro His Leu Cys Gly Leu Leu Val Phe Val ThrTrp Leu 140 145 150 Ile Gly Val Met Thr Ser Leu Leu His Ile Ser Leu MetMet His 155 160 165 Leu Ile Phe Cys Lys Asp Phe Glu Ile Pro His Phe PheCys Glu 170 175 180 Leu Thr Tyr Ile Leu Gln Leu Ala Cys Ser Asp Thr PheLeu Asn 185 190 195 Ser Thr Leu Ile Tyr Phe Met Thr Gly Val Leu Gly ValPhe Pro 200 205 210 Leu Leu Gly Ile Ile Phe Ser Tyr Ser Arg Ile Ala SerSer Ile 215 220 225 Arg Lys Met Ser Ser Ser Gly Gly Lys Gln Lys Ala LeuSer Thr 230 235 240 Cys Gly Ser His Leu Ser Val Val Ser Leu Phe Tyr GlyThr Gly 245 250 255 Ile Gly Val His Phe Thr Ser Ala Val Thr His Ser SerGln Lys 260 265 270 Ile Ser Val Ala Ser Val Met Tyr Thr Val Val Thr ProMet Leu 275 280 285 Asn Pro Phe Ile Tyr Ser Leu Arg Asn Lys Asp Val LysGly Ala 290 295 300 Leu Gly Ser Leu Leu Ser Arg Ala Ala Ser Cys Leu 305310 14 325 PRT Homo sapiens misc_feature Incyte ID No 7475695CD1 14 MetThr Thr Ile Ile Leu Glu Val Asp Asn His Thr Val Thr Thr 1 5 10 15 ArgPhe Ile Leu Leu Gly Phe Pro Thr Arg Pro Ala Phe Gln Leu 20 25 30 Leu PhePhe Ser Ile Phe Leu Ala Thr Tyr Leu Leu Thr Leu Leu 35 40 45 Glu Asn LeuLeu Ile Ile Leu Ala Ile His Ser Asp Gly Gln Leu 50 55 60 His Lys Pro MetTyr Phe Phe Leu Ser His Leu Ser Phe Leu Glu 65 70 75 Met Trp Tyr Val ThrVal Ile Ser Pro Lys Met Leu Val Asp Phe 80 85 90 Leu Ser His Asp Lys SerIle Ser Phe Asn Gly Cys Met Thr Gln 95 100 105 Leu Tyr Phe Phe Val ThrPhe Val Cys Thr Glu Tyr Ile Leu Leu 110 115 120 Ala Ile Met Ala Phe AspArg Tyr Val Ala Ile Cys Asn Pro Leu 125 130 135 Arg Tyr Pro Val Ile MetThr Asn Gln Leu Cys Gly Thr Leu Ala 140 145 150 Gly Gly Cys Trp Phe CysGly Leu Met Thr Ala Met Ile Lys Met 155 160 165 Val Phe Ile Ala Gln LeuHis Tyr Cys Gly Met Pro Gln Ile Asn 170 175 180 His Tyr Phe Cys Asp IleSer Pro Leu Leu Asn Val Ser Cys Glu 185 190 195 Asp Ala Ser Gln Ala GluMet Val Asp Phe Phe Leu Ala Leu Met 200 205 210 Val Ile Ala Ile Pro LeuCys Val Val Val Ala Ser Tyr Ala Ala 215 220 225 Ile Leu Ala Thr Ile LeuArg Ile Pro Ser Ala Gln Gly Arg Gln 230 235 240 Lys Ala Phe Ser Thr CysAla Ser His Leu Thr Val Val Ile Leu 245 250 255 Phe Tyr Ser Met Thr LeuPhe Thr Tyr Ala Arg Pro Lys Leu Met 260 265 270 Tyr Ala Tyr Asn Ser AsnLys Val Val Ser Val Leu Tyr Thr Val 275 280 285 Ile Val Pro Leu Leu AsnPro Ile Ile Tyr Cys Leu Arg Asn His 290 295 300 Glu Val Lys Ala Ala LeuArg Lys Thr Ile His Cys Arg Gly Ser 305 310 315 Gly Pro Gln Gly Asn GlyAla Phe Ser Ser 320 325 15 312 PRT Homo sapiens misc_feature Incyte IDNo 7477365CD1 15 Met Arg Gly Trp Asn His Thr Gly Ala Lys Glu Phe Leu LeuVal 1 5 10 15 Gly Leu Thr Glu Asn Pro Asn Leu Gln Ile Pro Leu Phe LeuLeu 20 25 30 Val Thr Leu Ile Tyr Phe Ile Thr Leu Leu Asp Asn Leu Gly Ile35 40 45 Ile Ile Leu Ile Trp Leu Asn Ala Gln Leu His Thr Pro Met Tyr 5055 60 Phe Phe Leu Gly Asn Leu Ser Phe Cys Asp Ile Cys Tyr Ser Thr 65 7075 Val Phe Ala Pro Lys Met Leu Val Asn Phe Leu Ser Lys His Lys 80 85 90Ser Ser Thr Phe Ser Gly Cys Val Leu Gln Ser Phe Pro Phe Ala 95 100 105Val Tyr Val Thr Thr Lys Asp Ile Leu Leu Ser Met Met Ala Tyr 110 115 120Asp His Tyr Val Ala Ile Ala Asn Pro Leu Leu Tyr Thr Val Ile 125 130 135Met Ala Gln Lys Val Cys Ile Gln Met Val Leu Ala Ser Tyr Leu 140 145 150Gly Gly Leu Ile Asn Ser Leu Thr His Thr Ile Gly Leu Leu Lys 155 160 165Leu Asp Phe Cys Gly Pro Asn Ile Val Asn His Tyr Phe Cys Asp 170 175 180Val Pro Pro Leu Leu Arg Leu Ser Cys Ser Asp Ala His Ile Asn 185 190 195Glu Met Leu Pro Leu Val Phe Ser Gly Leu Ile Ala Met Phe Thr 200 205 210Phe Ile Val Ile Met Val Ser Tyr Ile Cys Ile Ile Ile Ala Ile 215 220 225Gln Arg Ile His Ala Ala Glu Gly Arg Tyr Lys Ala Phe Ser Thr 230 235 240Cys Val Ser His Leu Thr Thr Val Thr Leu Phe Tyr Gly Ser Val 245 250 255Ser Phe Ser Tyr Ile Gln Pro Ser Ser Gln Tyr Ser Leu Glu Gln 260 265 270Glu Lys Val Leu Ala Val Phe Tyr Thr Leu Val Ile Pro Met Leu 275 280 285Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val Lys Asp Ala 290 295 300Ala Lys Arg Leu Ile Trp Trp Gly Lys Asn Pro Thr 305 310 16 324 PRT Homosapiens misc_feature Incyte ID No 7479899CD1 16 Met Glu Ala Arg Asn GlnThr Ala Ile Ser Lys Phe Leu Leu Leu 1 5 10 15 Gly Leu Ile Glu Asp ProGlu Leu Gln Pro Val Leu Phe Ser Leu 20 25 30 Phe Leu Ser Met Tyr Leu ValThr Ile Leu Gly Asn Leu Leu Ile 35 40 45 Leu Leu Ala Val Ile Ser Asp SerHis Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser Asn Leu Ser Phe LeuAsp Ile Cys Leu Ser Thr 65 70 75 Thr Thr Ile Pro Lys Met Leu Val Asn IleGln Ala Gln Asn Arg 80 85 90 Ser Ile Thr Tyr Ser Gly Cys Leu Thr Gln IleCys Phe Val Leu 95 100 105 Phe Phe Ala Gly Leu Glu Asn Cys Leu Leu AlaAla Met Ala Tyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys His Pro Leu ArgTyr Thr Val Ile 125 130 135 Met Asn Pro Arg Leu Cys Gly Leu Leu Ile LeuLeu Ser Leu Leu 140 145 150 Thr Ser Val Val Asn Ala Leu Leu Leu Ser LeuMet Val Leu Arg 155 160 165 Leu Ser Phe Cys Thr Asp Leu Glu Ile Pro LeuPhe Phe Cys Glu 170 175 180 Leu Ala Gln Val Ile Gln Leu Thr Cys Ser AspThr Leu Ile Asn 185 190 195 Asn Ile Leu Ile Tyr Phe Ala Ala Cys Ile PheGly Gly Val Pro 200 205 210 Leu Ser Gly Ile Ile Leu Ser Tyr Thr Gln IleThr Ser Cys Val 215 220 225 Leu Arg Met Pro Ser Ala Ser Gly Lys His LysAla Val Ser Thr 230 235 240 Cys Gly Ser His Leu Ser Ile Val Leu Leu PheTyr Gly Ala Gly 245 250 255 Leu Gly Val Tyr Ile Ser Ser Val Val Thr AspSer Pro Arg Lys 260 265 270 Thr Ala Val Ala Ser Val Met Tyr Ser Val PhePro Gln Met Val 275 280 285 Asn Pro Phe Ile Tyr Ser Leu Arg Asn Lys AspMet Lys Gly Thr 290 295 300 Leu Arg Lys Phe Ile Gly Arg Ile Pro Ser LeuLeu Trp Cys Ala 305 310 315 Ile Cys Phe Gly Phe Arg Phe Leu Glu 320 17314 PRT Homo sapiens misc_feature Incyte ID No 7480412CD1 17 Met Ala AsnHis Thr Gly Trp Ser Asp Phe Ile Leu Leu Gly Leu 1 5 10 15 Phe Arg GlnSer Lys His Pro Ala Leu Leu Cys Val Val Ile Phe 20 25 30 Val Val Phe LeuMet Ala Leu Ser Gly Asn Ala Val Leu Ile Leu 35 40 45 Leu Ile His Cys AspAla His Leu His Thr Pro Met Tyr Phe Phe 50 55 60 Ile Ser Gln Leu Ser LeuMet Asp Met Ala Tyr Ile Ser Val Thr 65 70 75 Val Pro Lys Met Leu Leu AspGln Val Met Gly Val Asn Lys Ile 80 85 90 Ser Ala Pro Glu Cys Gly Met GlnMet Phe Phe Tyr Val Thr Leu 95 100 105 Ala Gly Ser Glu Phe Phe Leu LeuAla Thr Met Ala Tyr Asp Arg 110 115 120 Tyr Val Ala Ile Cys His Pro LeuArg Tyr Pro Val Leu Met Asn 125 130 135 His Arg Val Cys Leu Phe Leu SerSer Gly Cys Trp Phe Leu Gly 140 145 150 Ser Val Asp Gly Phe Thr Phe ThrPro Ile Thr Met Thr Phe Pro 155 160 165 Phe Arg Gly Ser Arg Glu Ile HisHis Phe Phe Cys Glu Val Pro 170 175 180 Ala Val Leu Asn Leu Ser Cys SerAsp Thr Ser Leu Tyr Glu Ile 185 190 195 Phe Met Tyr Leu Cys Cys Val LeuMet Leu Leu Ile Pro Val Val 200 205 210 Ile Ile Ser Ser Ser Tyr Leu LeuIle Leu Leu Thr Ile His Gly 215 220 225 Met Asn Ser Ala Glu Gly Arg LysLys Ala Phe Ala Thr Cys Ser 230 235 240 Ser His Leu Thr Val Val Ile LeuPhe Tyr Gly Ala Ala Ile Tyr 245 250 255 Thr Tyr Met Leu Pro Ser Ser TyrHis Thr Pro Glu Lys Asp Met 260 265 270 Met Val Ser Val Phe Tyr Thr IleLeu Thr Pro Val Val Asn Pro 275 280 285 Leu Ile Tyr Ser Leu Arg Asn LysAsp Val Met Gly Ala Leu Lys 290 295 300 Lys Met Leu Thr Val Glu Pro AlaPhe Gln Lys Ala Met Glu 305 310 18 314 PRT Homo sapiens misc_featureIncyte ID No 7485460CD1 18 Met Glu Asn Asn Thr Glu Val Thr Glu Phe IleLeu Val Gly Leu 1 5 10 15 Thr Asp Asp Pro Glu Leu Gln Ile Pro Leu PheIle Val Phe Leu 20 25 30 Phe Ile Tyr Leu Ile Thr Leu Val Gly Asn Leu GlyMet Ile Glu 35 40 45 Leu Ile Leu Leu Asp Ser Cys Leu His Thr Pro Met TyrPhe Phe 50 55 60 Leu Ser Asn Leu Ser Leu Val Asp Phe Gly Tyr Ser Ser AlaVal 65 70 75 Thr Pro Lys Val Met Val Gly Phe Leu Thr Gly Asp Lys Phe Ile80 85 90 Leu Tyr Asn Ala Cys Ala Thr Gln Phe Phe Phe Phe Val Ala Phe 95100 105 Ile Thr Ala Glu Ser Phe Leu Leu Ala Ser Met Ala Tyr Asp Arg 110115 120 Tyr Ala Ala Leu Cys Lys Pro Leu His Tyr Thr Thr Thr Met Thr 125130 135 Thr Asn Val Cys Ala Cys Leu Ala Ile Gly Ser Tyr Ile Cys Gly 140145 150 Phe Leu Asn Ala Ser Ile His Thr Gly Asn Thr Phe Arg Leu Ser 155160 165 Phe Cys Arg Ser Asn Val Val Glu His Phe Phe Cys Asp Ala Pro 170175 180 Pro Leu Leu Thr Leu Ser Cys Ser Asp Asn Tyr Ile Ser Glu Met 185190 195 Val Ile Phe Phe Val Val Gly Phe Asn Asp Leu Phe Ser Ile Leu 200205 210 Val Ile Leu Ile Ser Tyr Leu Phe Ile Phe Ile Thr Ile Met Lys 215220 225 Met Arg Ser Pro Glu Gly Arg Gln Lys Ala Phe Ser Thr Cys Ala 230235 240 Ser His Leu Thr Ala Val Ser Ile Phe Tyr Gly Thr Gly Ile Phe 245250 255 Met Tyr Leu Arg Pro Asn Ser Ser His Phe Met Gly Thr Asp Lys 260265 270 Met Ala Ser Val Phe Tyr Ala Ile Val Ile Pro Met Leu Asn Pro 275280 285 Leu Val Tyr Ser Leu Arg Asn Lys Glu Val Lys Ser Ala Phe Lys 290295 300 Lys Thr Val Gly Lys Ala Lys Ala Ser Ile Gly Phe Ile Phe 305 31019 312 PRT Homo sapiens misc_feature Incyte ID No 7472173CD1 19 Met ArgAsn Gly Thr Val Ile Thr Glu Phe Ile Leu Leu Gly Phe 1 5 10 15 Pro ValIle Gln Gly Leu Gln Thr Pro Leu Phe Ile Ala Ile Phe 20 25 30 Leu Thr TyrIle Leu Thr Leu Ala Gly Asn Gly Leu Ile Ile Ala 35 40 45 Thr Val Trp AlaGlu Pro Arg Leu Gln Ile Pro Met Tyr Phe Phe 50 55 60 Leu Cys Asn Leu SerPhe Leu Glu Ile Trp Tyr Thr Thr Thr Val 65 70 75 Ile Pro Lys Leu Leu GlyThr Phe Val Val Ala Arg Thr Val Ile 80 85 90 Cys Met Ser Cys Cys Leu LeuGln Ala Phe Phe His Phe Phe Val 95 100 105 Gly Thr Thr Glu Phe Leu IleLeu Thr Ile Met Ser Phe Asp Arg 110 115 120 Tyr Leu Thr Ile Cys Asn ProLeu His His Pro Thr Ile Met Thr 125 130 135 Ser Lys Leu Cys Leu Gln LeuAla Leu Ser Ser Trp Val Val Gly 140 145 150 Phe Thr Ile Val Phe Cys GlnThr Met Leu Leu Ile Gln Leu Pro 155 160 165 Phe Cys Gly Asn Asn Val IleSer His Phe Tyr Cys Asp Val Gly 170 175 180 Pro Ser Leu Lys Ala Ala CysIle Asp Thr Ser Ile Leu Glu Leu 185 190 195 Leu Gly Val Ile Ala Thr IleLeu Val Ile Pro Gly Ser Leu Leu 200 205 210 Phe Asn Met Ile Ser Tyr IleTyr Ile Leu Ser Ala Ile Leu Arg 215 220 225 Ile Pro Ser Ala Thr Gly HisGln Lys Thr Phe Ser Thr Cys Ala 230 235 240 Ser His Leu Thr Val Val SerLeu Leu Tyr Gly Ala Val Leu Phe 245 250 255 Met Tyr Leu Arg Pro Thr AlaHis Ser Ser Phe Lys Ile Asn Lys 260 265 270 Val Val Ser Val Leu Asn ThrIle Leu Thr Pro Leu Leu Asn Pro 275 280 285 Phe Ile Tyr Thr Ile Arg AsnLys Glu Val Lys Gly Ala Leu Arg 290 295 300 Lys Ala Met Thr Cys Pro LysThr Gly His Ala Lys 305 310 20 312 PRT Homo sapiens misc_feature IncyteID No 7475690CD1 20 Met Glu Val Gly Asn Cys Thr Ile Leu Thr Glu Phe IleLeu Leu 1 5 10 15 Gly Phe Ser Ala Asp Ser Gln Trp Gln Pro Ile Leu PheGly Val 20 25 30 Phe Leu Met Leu Tyr Leu Ile Thr Leu Ser Gly Asn Met ThrLeu 35 40 45 Val Ile Leu Ile Arg Thr Asp Ser His Leu His Thr Pro Met Tyr50 55 60 Phe Phe Ile Gly Asn Leu Ser Phe Leu Asp Phe Trp Tyr Thr Ser 6570 75 Val Tyr Thr Pro Lys Ile Leu Ala Ser Cys Val Ser Glu Asp Lys 80 8590 Arg Ile Ser Leu Ala Gly Cys Gly Ala Gln Leu Phe Phe Ser Cys 95 100105 Val Val Ala Tyr Thr Glu Cys Tyr Leu Leu Ala Ala Met Ala Tyr 110 115120 Asp Arg His Ala Ala Ile Cys Asn Pro Leu Leu Tyr Ser Gly Thr 125 130135 Met Ser Thr Ala Leu Cys Thr Gly Leu Val Ala Gly Ser Tyr Ile 140 145150 Gly Gly Phe Leu Asn Ala Ile Ala His Thr Ala Asn Thr Phe Arg 155 160165 Leu His Phe Cys Gly Lys Asn Ile Ile Asp His Phe Phe Cys Asp 170 175180 Ala Pro Pro Leu Val Lys Met Ser Cys Thr Asn Thr Arg Val Tyr 185 190195 Glu Lys Val Leu Leu Gly Val Val Gly Phe Thr Val Leu Ser Ser 200 205210 Ile Leu Ala Ile Leu Ile Ser Tyr Val Asn Ile Leu Leu Ala Ile 215 220225 Leu Arg Ile His Ser Ala Ser Gly Arg His Lys Ala Phe Ser Thr 230 235240 Cys Ala Ser His Leu Ile Ser Val Met Leu Phe Tyr Gly Ser Leu 245 250255 Leu Phe Met Tyr Ser Arg Pro Ser Ser Thr Tyr Ser Leu Glu Arg 260 265270 Asp Lys Val Ala Ala Leu Phe Tyr Thr Val Ile Asn Pro Leu Leu 275 280285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Ile Lys Glu Ala 290 295300 Phe Arg Lys Ala Thr Gln Thr Ile Gln Pro Gln Thr 305 310 21 318 PRTHomo sapiens misc_feature Incyte ID No 7476068CD1 21 Met Pro Thr Val AsnHis Ser Gly Thr Ser His Thr Val Phe His 1 5 10 15 Leu Leu Gly Ile ProGly Leu Gln Asp Gln His Met Trp Ile Ser 20 25 30 Ile Pro Phe Phe Ile SerTyr Val Thr Ala Leu Leu Gly Asn Ser 35 40 45 Leu Leu Ile Phe Ile Ile LeuThr Lys Arg Ser Leu His Glu Pro 50 55 60 Met Tyr Leu Phe Leu Cys Met LeuAla Gly Ala Asp Ile Val Leu 65 70 75 Ser Thr Cys Thr Ile Pro Gln Ala LeuAla Ile Phe Trp Phe Arg 80 85 90 Ala Gly Asp Ile Ser Leu Asp Arg Cys IleThr Gln Leu Phe Phe 95 100 105 Ile His Ser Thr Phe Ile Ser Glu Ser GlyIle Leu Leu Val Met 110 115 120 Ala Phe Asp His Tyr Ile Ala Ile Cys TyrPro Leu Arg Tyr Thr 125 130 135 Thr Ile Leu Thr Asn Ala Leu Ile Lys LysIle Cys Val Thr Val 140 145 150 Ser Leu Arg Ser Tyr Gly Thr Ile Phe ProIle Ile Phe Leu Leu 155 160 165 Lys Arg Leu Thr Phe Cys Gln Asn Asn IleIle Pro His Thr Phe 170 175 180 Cys Glu His Ile Gly Leu Ala Lys Tyr AlaCys Asn Asp Ile Arg 185 190 195 Ile Asn Ile Trp Tyr Gly Phe Ser Ile LeuMet Ser Thr Val Val 200 205 210 Leu Asp Val Val Leu Ile Phe Ile Ser TyrMet Leu Ile Leu His 215 220 225 Ala Val Phe His Met Pro Ser Pro Asp AlaCys His Lys Ala Leu 230 235 240 Asn Thr Phe Gly Ser His Val Cys Ile IleIle Leu Phe Tyr Gly 245 250 255 Ser Gly Ile Phe Thr Ile Leu Thr Gln ArgPhe Gly Arg His Ile 260 265 270 Pro Pro Cys Ile His Ile Pro Leu Ala AsnVal Cys Ile Leu Ala 275 280 285 Pro Pro Met Leu Asn Pro Ile Ile Tyr GlyIle Lys Thr Lys Gln 290 295 300 Ile Gln Glu Gln Val Val Gln Phe Leu PheIle Lys Gln Lys Ile 305 310 315 Thr Leu Val 22 314 PRT Homo sapiensmisc_feature Incyte ID No 7476163CD1 22 Met Asp Gln Arg Asn Tyr Thr ArgVal Lys Glu Phe Thr Phe Leu 1 5 10 15 Gly Ile Thr Gln Ser Arg Glu LeuSer Gln Val Leu Phe Thr Phe 20 25 30 Leu Phe Leu Val Tyr Met Thr Thr LeuMet Gly Asn Phe Leu Ile 35 40 45 Met Val Thr Val Thr Cys Glu Ser His LeuHis Thr Pro Met Tyr 50 55 60 Phe Leu Leu Arg Asn Leu Ser Ile Leu Asp IleCys Phe Ser Ser 65 70 75 Ile Thr Ala Pro Lys Val Leu Ile Asp Leu Leu SerGlu Thr Lys 80 85 90 Thr Ile Ser Phe Ser Gly Cys Val Thr Gln Met Phe PhePhe His 95 100 105 Leu Leu Gly Gly Ala Asp Val Phe Ser Leu Ser Val MetAla Phe 110 115 120 Asp Arg Tyr Ile Ala Ile Ser Lys Pro Leu His Tyr MetThr Ile 125 130 135 Met Ser Arg Gly Arg Cys Thr Gly Leu Ile Val Gly PheLeu Gly 140 145 150 Gly Gly Leu Val His Ser Ile Ala Gln Ile Ser Leu LeuLeu Pro 155 160 165 Leu Pro Val Cys Gly Pro Asn Val Leu Asp Thr Phe TyrCys Asp 170 175 180 Val Pro Gln Val Leu Lys Leu Ala Cys Thr Asp Thr PheThr Leu 185 190 195 Glu Leu Leu Met Ile Ser Asn Asn Gly Leu Val Ser TrpPhe Val 200 205 210 Phe Phe Phe Leu Leu Ile Ser Tyr Thr Val Ile Leu MetMet Leu 215 220 225 Arg Ser His Thr Gly Glu Gly Arg Arg Lys Ala Ile SerThr Cys 230 235 240 Thr Ser His Ile Thr Val Val Thr Leu His Phe Val ProCys Ile 245 250 255 Tyr Val Tyr Ala Arg Pro Phe Thr Ala Leu Pro Thr AspThr Ala 260 265 270 Ile Ser Val Thr Phe Thr Val Ile Ser Pro Leu Leu AsnPro Ile 275 280 285 Ile Tyr Thr Leu Arg Asn Gln Glu Met Lys Leu Ala MetArg Lys 290 295 300 Leu Lys Arg Arg Leu Gly Gln Ser Glu Arg Ile Leu IleGln 305 310 23 311 PRT Homo sapiens misc_feature Incyte ID No 7476166CD123 Met Glu Met Glu Asn Cys Thr Arg Val Lys Glu Phe Ile Phe Leu 1 5 10 15Gly Leu Thr Gln Asn Arg Glu Val Ser Leu Val Leu Phe Leu Phe 20 25 30 LeuLeu Leu Val Tyr Val Thr Thr Leu Leu Gly Asn Leu Leu Ile 35 40 45 Met ValThr Val Thr Cys Glu Ser Arg Leu His Thr Pro Met Tyr 50 55 60 Phe Leu LeuHis Asn Leu Ser Ile Ala Asp Ile Cys Phe Ser Ser 65 70 75 Ile Thr Val ProLys Val Leu Val Asp Leu Leu Ser Glu Arg Lys 80 85 90 Thr Ile Ser Phe AsnHis Cys Phe Thr Gln Met Phe Leu Phe His 95 100 105 Leu Ile Gly Gly ValAsp Val Phe Ser Leu Ser Val Met Ala Leu 110 115 120 Asp Arg Tyr Val AlaIle Ser Lys Pro Leu His Tyr Ala Thr Ile 125 130 135 Met Ser Arg Asp HisCys Ile Gly Leu Thr Val Ala Ala Trp Leu 140 145 150 Gly Gly Phe Val HisSer Ile Val Gln Ile Ser Leu Leu Leu Pro 155 160 165 Leu Pro Phe Cys GlyPro Asn Val Leu Asp Thr Phe Tyr Cys Asp 170 175 180 Val His Arg Val LeuLys Leu Ala His Thr Asp Ile Phe Ile Leu 185 190 195 Glu Leu Leu Met IleSer Asn Asn Gly Leu Leu Thr Thr Leu Trp 200 205 210 Phe Phe Leu Leu LeuVal Ser Tyr Ile Val Ile Leu Ser Leu Pro 215 220 225 Lys Ser Gln Ala GlyGlu Gly Arg Arg Lys Ala Ile Ser Thr Cys 230 235 240 Thr Ser His Ile ThrVal Val Thr Leu His Phe Val Pro Cys Ile 245 250 255 Tyr Val Tyr Ala ArgPro Phe Thr Ala Leu Pro Met Asp Lys Ala 260 265 270 Ile Ser Val Thr PheThr Val Ile Ser Pro Leu Leu Asn Pro Leu 275 280 285 Ile Tyr Thr Leu ArgAsn His Glu Met Lys Ser Ala Met Arg Arg 290 295 300 Leu Lys Arg Arg LeuVal Pro Ser Asp Arg Lys 305 310 24 312 PRT Homo sapiens misc_featureIncyte ID No 7476686CD1 24 Met Asp Leu Lys Asn Gly Ser Leu Val Thr GluPhe Ile Leu Leu 1 5 10 15 Gly Phe Phe Gly Arg Trp Glu Leu Gln Ile PhePhe Phe Val Thr 20 25 30 Phe Ser Leu Ile Tyr Gly Ala Thr Val Met Gly AsnIle Leu Ile 35 40 45 Met Val Thr Val Thr Cys Arg Ser Thr Leu His Ser ProLeu Tyr 50 55 60 Phe Leu Leu Gly Asn Leu Ser Phe Leu Asp Met Cys Leu SerThr 65 70 75 Ala Thr Thr Pro Lys Met Ile Ile Asp Leu Leu Thr Asp His Lys80 85 90 Thr Ile Ser Val Trp Gly Cys Val Thr Gln Met Phe Phe Met His 95100 105 Phe Phe Gly Gly Ala Glu Met Thr Leu Leu Ile Ile Met Ala Phe 110115 120 Asp Arg Tyr Val Ala Ile Cys Lys Pro Leu His Tyr Arg Thr Ile 125130 135 Met Ser His Lys Leu Leu Lys Gly Phe Ala Ile Leu Ser Trp Ile 140145 150 Ile Gly Phe Leu His Ser Ile Ser Gln Ile Val Leu Thr Met Asn 155160 165 Leu Pro Phe Cys Gly His Asn Val Ile Asn Asn Ile Phe Cys Asp 170175 180 Leu Pro Leu Val Ile Lys Leu Ala Cys Ile Glu Thr Tyr Thr Leu 185190 195 Glu Leu Phe Val Ile Ala Asp Ser Gly Leu Leu Ser Phe Thr Cys 200205 210 Phe Ile Leu Leu Leu Val Ser Tyr Ile Val Ile Leu Val Ser Val 215220 225 Pro Lys Lys Ser Ser His Gly Leu Ser Lys Ala Leu Ser Thr Leu 230235 240 Ser Ala His Ile Ile Val Val Thr Leu Phe Phe Gly Pro Cys Ile 245250 255 Phe Ile Tyr Val Trp Pro Phe Ser Ser Leu Ala Ser Asn Lys Thr 260265 270 Leu Ala Val Phe Tyr Thr Val Ile Thr Pro Leu Leu Asn Pro Ser 275280 285 Ile Tyr Thr Leu Arg Asn Lys Lys Met Gln Glu Ala Ile Arg Lys 290295 300 Leu Arg Phe Gln Tyr Val Ser Ser Ala Gln Asn Phe 305 310 25 324PRT Homo sapiens misc_feature Incyte ID No 7477363CD1 25 Met Leu Glu SerAsn Tyr Thr Met Pro Thr Glu Phe Leu Phe Val 1 5 10 15 Gly Phe Thr AspTyr Leu Pro Leu Arg Val Thr Leu Phe Leu Val 20 25 30 Phe Leu Leu Val TyrThr Leu Thr Met Val Gly Asn Ile Leu Leu 35 40 45 Ile Ile Leu Val Asn IleAsn Ser Ser Leu Gln Ile Pro Met Tyr 50 55 60 Tyr Phe Leu Ser Asn Leu SerPhe Leu Asp Ile Ser Cys Ser Thr 65 70 75 Ala Ile Thr Pro Lys Met Leu AlaAsn Phe Leu Ala Ser Arg Lys 80 85 90 Ser Ile Ser Pro Tyr Gly Cys Ala LeuGln Met Phe Phe Phe Ala 95 100 105 Ser Phe Ala Asp Ala Glu Cys Leu IleLeu Ala Ala Met Ala Tyr 110 115 120 Asp Arg Tyr Ala Ala Ile Cys Asn ProLeu Leu Tyr Thr Thr Leu 125 130 135 Met Ser Arg Arg Val Cys Val Cys PheIle Val Leu Ala Tyr Phe 140 145 150 Ser Gly Ser Thr Thr Ser Leu Val HisVal Cys Leu Thr Phe Arg 155 160 165 Leu Ser Phe Cys Gly Ser Asn Ile ValAsn His Phe Phe Cys Asp 170 175 180 Ile Pro Pro Leu Leu Ala Leu Ser CysThr Asp Thr Gln Ile Asn 185 190 195 Gln Leu Leu Leu Phe Ala Leu Cys SerPhe Ile Gln Thr Ser Thr 200 205 210 Phe Val Val Ile Phe Ile Ser Tyr PheCys Ile Leu Ile Thr Val 215 220 225 Leu Ser Ile Lys Ser Ser Gly Gly ArgSer Lys Thr Phe Ser Thr 230 235 240 Cys Ala Ser His Leu Ile Ala Val ThrLeu Phe Tyr Gly Ala Leu 245 250 255 Leu Phe Met Tyr Leu Gln Pro Thr ThrSer Tyr Ser Leu Asp Thr 260 265 270 Asp Lys Val Val Ala Val Phe Tyr ThrVal Val Phe Pro Met Phe 275 280 285 Asn Pro Ile Ile Tyr Ser Phe Arg AsnLys Asp Val Lys Asn Ala 290 295 300 Leu Lys Lys Leu Leu Glu Arg Ile GlyTyr Ser Asn Glu Trp Tyr 305 310 315 Leu Asn Arg Leu Arg Ile Val Asn Ile320 26 325 PRT Homo sapiens misc_feature Incyte ID No 7477368CD1 26 MetLeu Glu Ser Phe Gln Lys Ser Glu Gln Met Ala Trp Ser Asn 1 5 10 15 GlnSer Ala Val Thr Glu Phe Ile Leu Arg Gly Leu Ser Ser Ser 20 25 30 Leu GluLeu Gln Ile Phe Tyr Phe Leu Phe Phe Ser Ile Val Tyr 35 40 45 Ala Ala ThrVal Leu Gly Asn Leu Leu Ile Val Val Thr Ile Ala 50 55 60 Ser Glu Pro HisLeu His Ser Pro Met Tyr Phe Leu Leu Gly Asn 65 70 75 Leu Ser Phe Ile AspMet Ser Leu Ala Ser Phe Ala Thr Pro Lys 80 85 90 Met Ile Ala Asp Phe LeuArg Glu His Lys Ala Ile Ser Phe Glu 95 100 105 Gly Cys Met Thr Gln MetPhe Phe Leu His Leu Leu Gly Gly Ala 110 115 120 Glu Ile Val Leu Leu IleSer Met Ser Phe Asp Arg Tyr Val Ala 125 130 135 Ile Cys Lys Pro Leu HisTyr Leu Thr Ile Met Ser Arg Arg Met 140 145 150 Cys Val Gly Leu Val IleLeu Ser Trp Ile Val Gly Ile Phe His 155 160 165 Ala Leu Ser Gln Leu AlaPhe Thr Val Asn Leu Pro Phe Cys Gly 170 175 180 Pro Asn Glu Val Asp SerPhe Phe Cys Asp Leu Pro Leu Val Ile 185 190 195 Lys Leu Ala Cys Val AspThr Tyr Ile Leu Gly Val Phe Met Ile 200 205 210 Ser Thr Ser Gly Met IleAla Leu Val Cys Phe Ile Leu Leu Val 215 220 225 Ile Ser Tyr Thr Ile IleLeu Val Thr Val Arg Gln Arg Ser Ser 230 235 240 Gly Gly Ser Ser Lys AlaLeu Ser Thr Cys Ser Ala His Phe Thr 245 250 255 Val Val Thr Leu Phe PheGly Pro Cys Thr Phe Ile Tyr Val Trp 260 265 270 Pro Phe Thr Asn Phe ProIle Asp Lys Val Leu Ser Val Phe Tyr 275 280 285 Thr Ile Tyr Thr Pro LeuLeu Asn Pro Val Ile Tyr Thr Val Arg 290 295 300 Asn Lys Asp Val Lys TyrSer Met Arg Lys Leu Ser Ser His Ile 305 310 315 Phe Lys Ser Arg Lys ThrAsp His Thr Pro 320 325 27 317 PRT Homo sapiens misc_feature Incyte IDNo 7480408CD1 27 Met Glu Gln Ser Asn Tyr Ser Val Tyr Ala Asp Phe Ile LeuLeu 1 5 10 15 Gly Leu Phe Ser Asn Ala Arg Phe Pro Trp Leu Leu Phe AlaLeu 20 25 30 Ile Leu Leu Val Phe Leu Thr Ser Ile Ala Ser Asn Val Val Lys35 40 45 Ile Ile Leu Ile His Ile Asp Ser Arg Leu His Thr Pro Met Tyr 5055 60 Phe Leu Leu Ser Gln Leu Ser Leu Arg Asp Ile Leu Tyr Ile Ser 65 7075 Thr Ile Val Pro Lys Met Leu Val Asp Gln Val Met Ser Gln Arg 80 85 90Ala Ile Ser Phe Ala Gly Cys Thr Ala Gln His Phe Leu Tyr Leu 95 100 105Thr Leu Ala Gly Ala Glu Phe Phe Leu Leu Gly Leu Met Ser Tyr 110 115 120Asp Arg Tyr Val Ala Ile Cys Asn Pro Leu His Tyr Pro Val Leu 125 130 135Met Ser Arg Lys Ile Cys Trp Leu Ile Val Ala Ala Ala Trp Leu 140 145 150Gly Gly Ser Ile Asp Gly Phe Leu Leu Thr Pro Val Thr Met Gln 155 160 165Phe Pro Phe Cys Ala Ser Arg Glu Ile Asn His Phe Phe Cys Glu 170 175 180Val Pro Ala Leu Leu Lys Leu Ser Cys Thr Asp Thr Ser Ala Tyr 185 190 195Glu Thr Ala Met Tyr Val Cys Cys Ile Met Met Leu Leu Ile Pro 200 205 210Phe Ser Val Ile Ser Gly Ser Tyr Thr Arg Ile Leu Ile Thr Val 215 220 225Tyr Arg Met Ser Glu Ala Glu Gly Arg Gly Lys Ala Val Ala Thr 230 235 240Cys Ser Ser His Met Val Val Val Ser Leu Phe Tyr Gly Ala Ala 245 250 255Met Tyr Thr Tyr Val Leu Pro His Ser Tyr His Thr Pro Glu Gln 260 265 270Asp Lys Ala Val Ser Ala Phe Tyr Thr Ile Leu Thr Pro Met Leu 275 280 285Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val Thr Gly Ala 290 295 300Leu Gln Lys Val Val Gly Arg Cys Val Ser Ser Gly Lys Val Thr 305 310 315Thr Phe 28 312 PRT Homo sapiens misc_feature Incyte ID No 7480409CD1 28Met Pro Asn Ser Thr Thr Val Met Glu Phe Leu Leu Met Arg Phe 1 5 10 15Ser Asp Val Trp Thr Leu Gln Ile Leu His Ser Ala Ser Phe Phe 20 25 30 MetLeu Tyr Leu Val Thr Leu Met Gly Asn Ile Leu Ile Val Thr 35 40 45 Val ThrThr Cys Asp Ser Ser Leu His Met Pro Met Tyr Phe Phe 50 55 60 Leu Arg AsnLeu Ser Ile Leu Asp Ala Cys Tyr Ile Ser Val Thr 65 70 75 Val Pro Thr SerCys Val Asn Ser Leu Leu Asp Ser Thr Thr Ile 80 85 90 Ser Lys Ala Gly CysVal Ala Gln Val Phe Leu Val Val Phe Phe 95 100 105 Val Tyr Val Glu LeuLeu Phe Leu Thr Ile Met Ala His Asp Arg 110 115 120 Tyr Val Ala Val CysGln Pro Leu His Tyr Pro Val Ile Val Asn 125 130 135 Ser Arg Ile Cys IleGln Met Thr Leu Ala Ser Leu Leu Ser Gly 140 145 150 Leu Val Tyr Ala GlyMet His Thr Gly Ser Thr Phe Gln Leu Pro 155 160 165 Phe Cys Arg Ser AsnVal Ile His Gln Phe Phe Cys Asp Ile Pro 170 175 180 Ser Leu Leu Lys LeuSer Cys Ser Asp Thr Phe Ser Asn Glu Val 185 190 195 Met Ile Val Val SerAla Leu Gly Val Gly Gly Gly Cys Phe Ile 200 205 210 Phe Ile Ile Arg SerTyr Ile His Ile Phe Ser Thr Val Leu Gly 215 220 225 Phe Pro Arg Gly AlaAsp Arg Thr Lys Ala Phe Ser Thr Cys Ile 230 235 240 Pro His Ile Leu ValVal Ser Val Phe Leu Ser Ser Cys Ser Ser 245 250 255 Val Tyr Leu Arg ProPro Ala Ile Pro Ala Ala Thr Gln Asp Leu 260 265 270 Ile Leu Ser Gly PheTyr Ser Ile Met Pro Pro Leu Phe Asn Pro 275 280 285 Ile Ile Tyr Ser LeuArg Asn Lys Gln Ile Lys Val Ala Ile Lys 290 295 300 Lys Ile Met Lys ArgIle Phe Tyr Ser Glu Asn Val 305 310 29 316 PRT Homo sapiens misc_featureIncyte ID No 7482487CD1 29 Met Thr Asn Thr Ser Ser Ser Asp Phe Thr LeuLeu Gly Leu Leu 1 5 10 15 Val Asn Ser Glu Ala Ala Gly Ile Val Phe ThrVal Ile Leu Ala 20 25 30 Val Phe Leu Gly Ala Val Thr Ala Asn Leu Val MetIle Phe Leu 35 40 45 Ile Gln Val Asp Ser Arg Leu His Thr Pro Met Tyr PheLeu Leu 50 55 60 Ser Gln Leu Ser Ile Met Asp Thr Leu Phe Ile Cys Thr ThrVal 65 70 75 Pro Lys Leu Leu Ala Asp Met Val Ser Lys Glu Lys Ile Ile Ser80 85 90 Phe Val Ala Cys Gly Ile Gln Ile Phe Leu Tyr Leu Thr Met Ile 95100 105 Gly Ser Glu Phe Phe Leu Leu Gly Leu Met Ala Tyr Asp Cys Tyr 110115 120 Val Ala Val Cys Asn Pro Leu Arg Tyr Pro Val Leu Met Asn Arg 125130 135 Lys Lys Cys Leu Leu Leu Ala Ala Gly Ala Trp Phe Gly Gly Ser 140145 150 Leu Asp Gly Phe Leu Leu Thr Pro Ile Thr Met Asn Val Pro Tyr 155160 165 Cys Gly Ser Arg Ser Ile Asn His Phe Phe Cys Glu Ile Pro Ala 170175 180 Val Leu Lys Leu Ala Cys Ala Asp Thr Ser Leu Tyr Glu Thr Leu 185190 195 Met Tyr Ile Cys Cys Val Leu Met Leu Leu Ile Pro Ile Ser Ile 200205 210 Ile Ser Thr Ser Tyr Ser Leu Ile Leu Leu Thr Ile His Arg Met 215220 225 Pro Ser Ala Glu Gly Arg Lys Lys Ala Phe Thr Thr Cys Ser Ser 230235 240 His Leu Thr Val Val Ser Ile Phe Tyr Gly Ala Ala Phe Tyr Thr 245250 255 Tyr Val Leu Pro Gln Ser Phe His Thr Pro Glu Gln Asp Lys Val 260265 270 Val Ser Ala Phe Tyr Thr Ile Val Thr Pro Met Leu Asn Pro Leu 275280 285 Ile Tyr Ser Leu Arg Asn Lys Asp Val Ile Gly Ala Phe Lys Lys 290295 300 Val Phe Ala Cys Cys Ser Ser Ala Gln Lys Val Ala Thr Ser Asp 305310 315 Ala 30 314 PRT Homo sapiens misc_feature Incyte ID No 7485424CD130 Met Ala Arg Lys Asp Met Ala His Ile Asn Cys Thr Gln Ala Thr 1 5 10 15Glu Phe Ile Leu Val Gly Leu Thr Asp His Gln Glu Leu Lys Met 20 25 30 ProLeu Phe Val Leu Phe Leu Ser Ile Tyr Leu Phe Thr Val Val 35 40 45 Gly AsnLeu Gly Leu Ile Leu Leu Ile Arg Ala Asp Thr Ser Leu 50 55 60 Asn Thr ProMet Tyr Phe Phe Leu Ser Asn Leu Ala Phe Val Asp 65 70 75 Phe Cys Tyr SerSer Val Ile Thr Pro Lys Met Leu Gly Asn Phe 80 85 90 Leu Tyr Lys Gln AsnVal Ile Ser Phe Asp Ala Cys Ala Thr Gln 95 100 105 Leu Gly Cys Phe LeuThr Phe Met Ile Ser Glu Ser Leu Leu Leu 110 115 120 Ala Ser Met Ala TyrAsp Arg Tyr Val Ala Ile Cys Asn Pro Leu 125 130 135 Leu Tyr Met Val ValMet Thr Pro Gly Ile Cys Ile Gln Leu Val 140 145 150 Ala Val Pro Tyr SerTyr Ser Phe Leu Met Ala Leu Phe His Thr 155 160 165 Ile Leu Thr Phe ArgLeu Ser Tyr Cys His Ser Asn Ile Val Asn 170 175 180 His Phe Tyr Cys AspAsp Met Pro Leu Leu Arg Leu Thr Cys Ser 185 190 195 Asp Thr Arg Phe LysGln Leu Trp Ile Phe Ala Cys Ala Gly Ile 200 205 210 Met Phe Ile Ser SerLeu Leu Ile Val Phe Val Ser Tyr Met Phe 215 220 225 Ile Ile Ser Ala IleLeu Arg Met His Ser Ala Glu Gly Arg Gln 230 235 240 Lys Ala Phe Ser ThrCys Gly Ser His Met Leu Ala Val Thr Ile 245 250 255 Phe Tyr Gly Thr LeuIle Phe Met Tyr Leu Gln Pro Ser Ser Ser 260 265 270 His Ala Leu Asp ThrAsp Lys Met Ala Ser Val Phe Tyr Thr Val 275 280 285 Ile Ile Pro Met LeuAsn Pro Leu Ile Tyr Ser Leu Gln Asn Lys 290 295 300 Glu Val Lys Glu AlaLeu Lys Lys Ile Ile Ile Asn Lys Asn 305 310 31 321 PRT Homo sapiensmisc_feature Incyte ID No 7475196CD1 31 Met Thr Ile Leu Leu Asn Ser SerLeu Gln Arg Ala Thr Phe Phe 1 5 10 15 Leu Thr Gly Phe Gln Gly Leu GluGly Leu His Gly Trp Ile Ser 20 25 30 Ile Pro Phe Cys Phe Ile Tyr Leu ThrVal Ile Leu Gly Asn Leu 35 40 45 Thr Ile Leu His Val Ile Cys Thr Asp AlaThr Leu His Gly Pro 50 55 60 Met Tyr Tyr Phe Leu Gly Met Leu Ala Val ThrAsp Leu Gly Leu 65 70 75 Cys Leu Ser Thr Leu Pro Thr Val Leu Gly Ile PheTrp Phe Asp 80 85 90 Thr Arg Glu Ile Gly Ile Pro Ala Cys Phe Thr Gln LeuPhe Phe 95 100 105 Ile His Thr Leu Ser Ser Met Glu Ser Ser Val Leu LeuSer Met 110 115 120 Ser Ile Asp Arg Tyr Val Ala Val Cys Asn Pro Leu HisAsp Ser 125 130 135 Thr Val Leu Thr Pro Ala Cys Ile Val Lys Met Gly LeuSer Ser 140 145 150 Val Leu Arg Ser Ala Leu Leu Ile Leu Pro Leu Pro PheLeu Leu 155 160 165 Lys Arg Phe Gln Tyr Cys His Ser His Val Leu Ala HisAla Tyr 170 175 180 Cys Leu His Leu Glu Ile Met Lys Leu Ala Cys Ser SerIle Ile 185 190 195 Val Asn His Ile Tyr Gly Leu Phe Val Val Ala Cys ThrVal Gly 200 205 210 Val Asp Ser Leu Leu Ile Phe Leu Ser Tyr Ala Leu IleLeu Arg 215 220 225 Thr Val Leu Ser Ile Ala Ser His Gln Glu Arg Leu ArgAla Leu 230 235 240 Asn Thr Cys Val Ser His Ile Cys Ala Val Leu Leu PheTyr Ile 245 250 255 Pro Met Ile Gly Leu Ser Leu Val His Arg Phe Gly GluHis Leu 260 265 270 Pro Arg Val Val His Leu Phe Met Ser Tyr Val Tyr LeuLeu Val 275 280 285 Pro Pro Leu Met Asn Pro Ile Ile Tyr Ser Ile Lys ThrLys Gln 290 295 300 Ile Arg Gln Arg Ile Ile Lys Lys Phe Gln Phe Ile LysSer Leu 305 310 315 Arg Cys Phe Trp Lys Asp 320 32 311 PRT Homo sapiensmisc_feature Incyte ID No 7475295CD1 32 Met Gly Lys Glu Asn Cys Thr ThrVal Ala Glu Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser Asp Val Pro Glu LeuArg Val Cys Leu Phe Leu Leu 20 25 30 Phe Leu Leu Ile Tyr Gly Val Thr LeuLeu Ala Asn Leu Gly Met 35 40 45 Ile Ala Leu Ile Gln Val Ser Ser Arg LeuHis Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser His Leu Ser Ser Val Asp PheCys Tyr Ser Ser 65 70 75 Ile Ile Val Pro Lys Met Leu Ala Asn Ile Phe AsnLys Asp Lys 80 85 90 Ala Ile Ser Phe Leu Gly Cys Met Val Gln Phe Tyr LeuPhe Cys 95 100 105 Thr Cys Val Val Thr Glu Val Phe Leu Leu Ala Val MetAla Tyr 110 115 120 Asp Arg Phe Val Ala Ile Cys Asn Pro Leu Leu Tyr ThrVal Thr 125 130 135 Met Ser Trp Lys Val Arg Val Glu Leu Ala Ser Cys CysTyr Phe 140 145 150 Cys Gly Thr Val Cys Ser Leu Ile His Leu Cys Leu AlaLeu Arg 155 160 165 Ile Pro Phe Tyr Arg Ser Asn Val Ile Asn His Phe PheCys Asp 170 175 180 Leu Pro Pro Val Leu Ser Leu Ala Cys Ser Asp Ile ThrVal Asn 185 190 195 Glu Thr Leu Leu Phe Leu Val Ala Thr Leu Asn Glu SerVal Thr 200 205 210 Ile Met Ile Ile Leu Thr Ser Tyr Leu Leu Ile Leu ThrThr Ile 215 220 225 Leu Lys Met Gly Ser Ala Glu Gly Arg His Lys Ala PheSer Thr 230 235 240 Cys Ala Ser His Leu Thr Ala Ile Thr Val Phe His GlyThr Val 245 250 255 Leu Ser Ile Tyr Cys Arg Pro Ser Ser Gly Asn Ser GlyAsp Ala 260 265 270 Asp Lys Val Ala Thr Val Phe Tyr Thr Val Val Ile ProMet Leu 275 280 285 Asn Ser Val Ile Tyr Ser Leu Arg Asn Lys Asp Val LysGlu Ala 290 295 300 Leu Arg Lys Val Met Gly Ser Lys Ile His Ser 305 31033 311 PRT Homo sapiens misc_feature Incyte ID No 7478361CD1 33 Met GlySer Phe Asn Thr Ser Phe Glu Asp Gly Phe Ile Leu Val 1 5 10 15 Gly PheSer Asp Trp Pro Gln Leu Glu Pro Ile Leu Phe Val Phe 20 25 30 Ile Phe IlePhe Tyr Ser Leu Thr Leu Phe Gly Asn Thr Ile Ile 35 40 45 Ile Ala Leu SerTrp Leu Asp Leu Arg Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser HisLeu Ser Leu Leu Asp Leu Cys Phe Thr Thr 65 70 75 Ser Thr Val Pro Gln LeuLeu Ile Asn Leu Cys Gly Val Asp Arg 80 85 90 Thr Ile Thr Arg Gly Gly CysVal Ala Gln Leu Phe Ile Tyr Leu 95 100 105 Ala Leu Gly Ser Thr Glu CysVal Leu Leu Val Val Met Ala Phe 110 115 120 Asp Arg Tyr Ala Ala Val CysArg Pro Leu His Tyr Met Ala Ile 125 130 135 Met His Pro His Leu Cys GlnThr Leu Ala Ile Ala Ser Trp Gly 140 145 150 Ala Gly Phe Val Asn Ser LeuIle Gln Thr Gly Leu Ala Met Ala 155 160 165 Met Pro Leu Cys Gly His ArgLeu Asn His Phe Phe Cys Glu Met 170 175 180 Pro Val Phe Leu Lys Leu AlaCys Ala Asp Thr Glu Gly Thr Glu 185 190 195 Ala Lys Met Phe Val Ala ArgVal Ile Val Val Ala Val Pro Ala 200 205 210 Ala Leu Ile Leu Gly Ser TyrVal His Ile Ala His Ala Val Leu 215 220 225 Arg Val Lys Ser Thr Ala GlyArg Arg Lys Ala Phe Gly Thr Cys 230 235 240 Gly Ser His Leu Leu Val ValPhe Leu Phe Tyr Gly Ser Ala Ile 245 250 255 Tyr Thr Tyr Leu Gln Ser IleHis Asn Tyr Ser Glu Arg Glu Gly 260 265 270 Lys Phe Val Ala Leu Phe TyrThr Ile Ile Thr Pro Ile Leu Asn 275 280 285 Pro Leu Ile Tyr Thr Leu ArgAsn Lys Asp Val Lys Gly Ala Leu 290 295 300 Trp Lys Val Leu Trp Arg GlyArg Asp Ser Gly 305 310 34 312 PRT Homo sapiens misc_feature Incyte IDNo 7482534CD1 34 Met Glu Val Lys Asn Cys Cys Met Val Thr Glu Phe Ile LeuLeu 1 5 10 15 Gly Ile Pro His Thr Glu Gly Leu Glu Met Thr Leu Phe ValLeu 20 25 30 Phe Leu Pro Phe Tyr Ala Cys Thr Leu Leu Gly Asn Val Ser Ile35 40 45 Leu Val Ala Val Met Ser Ser Ala Arg Leu His Thr Pro Met Tyr 5055 60 Phe Phe Leu Gly Asn Leu Ser Val Phe Asp Met Gly Phe Ser Ser 65 7075 Val Thr Cys Pro Lys Met Leu Leu Tyr Leu Met Gly Leu Ser Arg 80 85 90Leu Ile Ser Tyr Lys Asp Cys Val Cys Gln Leu Phe Phe Phe His 95 100 105Phe Leu Gly Ser Ile Glu Cys Phe Leu Phe Thr Val Met Ala Tyr 110 115 120Asp Arg Phe Thr Ala Ile Cys Tyr Pro Leu Arg Tyr Thr Val Ile 125 130 135Met Asn Pro Arg Ile Cys Val Ala Leu Ala Val Gly Thr Trp Leu 140 145 150Leu Gly Cys Ile His Ser Ser Ile Leu Thr Ser Leu Thr Phe Thr 155 160 165Leu Pro Tyr Cys Gly Pro Asn Glu Val Asp His Phe Phe Cys Asp 170 175 180Ile Pro Ala Leu Leu Pro Leu Ala Cys Ala Asp Thr Ser Leu Ala 185 190 195Gln Arg Val Ser Phe Thr Asn Val Gly Leu Ile Ser Leu Val Cys 200 205 210Phe Leu Leu Ile Leu Leu Ser Tyr Thr Arg Ile Thr Ile Ser Ile 215 220 225Leu Ser Ile Arg Thr Thr Glu Gly Arg Arg Arg Ala Phe Ser Thr 230 235 240Cys Ser Ala His Leu Ile Ala Ile Leu Cys Ala Tyr Gly Pro Ile 245 250 255Ile Thr Val Tyr Leu Gln Pro Thr Pro Asn Pro Met Leu Gly Thr 260 265 270Val Val Gln Ile Leu Met Asn Leu Val Gly Pro Met Leu Asn Pro 275 280 285Leu Ile Tyr Thr Leu Arg Asn Lys Glu Val Lys Thr Ala Leu Lys 290 295 300Thr Ile Leu His Arg Thr Gly His Val Pro Glu Ser 305 310 35 314 PRT Homosapiens misc_feature Incyte ID No 7490493CD1 35 Met Lys Arg Gln Asn GlnSer Cys Val Val Glu Phe Ile Leu Leu 1 5 10 15 Gly Phe Ser Asn Phe ProGlu Leu Gln Val Gln Leu Phe Gly Val 20 25 30 Phe Leu Val Ile Tyr Val ValThr Leu Met Gly Asn Ala Ile Ile 35 40 45 Thr Val Ile Ile Ser Leu Asn GlnSer Leu His Val Pro Met Tyr 50 55 60 Leu Phe Leu Leu Asn Leu Ser Val ValGlu Val Ser Phe Ser Ala 65 70 75 Val Ile Thr Pro Glu Met Leu Val Val LeuSer Thr Glu Lys Thr 80 85 90 Met Ile Ser Phe Val Gly Cys Phe Ala Gln MetTyr Phe Ile Leu 95 100 105 Leu Phe Gly Gly Thr Glu Cys Phe Leu Leu GlyAla Met Ala Tyr 110 115 120 Asp Arg Phe Ala Ala Ile Cys His Pro Leu AsnTyr Pro Val Ile 125 130 135 Met Asn Arg Gly Val Phe Met Lys Leu Val IlePhe Ser Trp Ala 140 145 150 Leu Gly Phe Met Leu Gly Thr Val Gln Thr SerTrp Val Ser Ser 155 160 165 Phe Pro Phe Cys Gly Leu Asn Glu Ile Asn HisIle Ser Cys Glu 170 175 180 Thr Pro Ala Val Leu Glu Leu Ala Cys Ala AspThr Phe Leu Phe 185 190 195 Glu Ile Tyr Ala Phe Thr Gly Thr Ile Leu IleVal Met Val Pro 200 205 210 Phe Leu Leu Ile Leu Leu Ser Tyr Ile Arg ValLeu Phe Ala Ile 215 220 225 Leu Lys Met Pro Ser Thr Thr Gly Arg Gln LysAla Phe Ser Thr 230 235 240 Cys Ala Ser His Leu Thr Ser Val Thr Leu PheTyr Gly Thr Ala 245 250 255 Asn Met Thr Tyr Leu Gln Pro Lys Ser Gly TyrSer Pro Glu Thr 260 265 270 Lys Lys Leu Ile Ser Leu Ala Tyr Thr Leu LeuThr Pro Leu Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Ser GluMet Lys Arg Thr 290 295 300 Leu Ile Lys Leu Trp Arg Arg Lys Val Ile LeuHis Thr Phe 305 310 36 393 PRT Homo sapiens misc_feature Incyte ID No58001274CD1 36 Met Glu Val Glu Gly Leu Gln Asn Thr Glu Ala Lys Tyr HisAsp 1 5 10 15 Ser Ser Glu Leu Thr Glu Gly Ala Thr Ala Gln His Val ThrPhe 20 25 30 Trp Ala Thr Asp Thr Ile Glu His Val Thr Gln Ala Phe Val Ser35 40 45 Met Ala Thr Gly Leu Gln Glu Gly Tyr Gly Gln Thr Asp Ile Asp 5055 60 Ser Val Leu Gly Ile Phe Leu Arg Lys Asp Leu Leu Glu Ile Met 65 7075 Leu Gln Gln Lys Val Phe Met Glu Lys Trp Asn His Thr Ser Asn 80 85 90Asp Phe Ile Leu Leu Gly Leu Leu Pro Pro Asn Gln Thr Gly Ile 95 100 105Phe Leu Leu Cys Leu Ile Ile Leu Ile Phe Phe Leu Ala Ser Val 110 115 120Gly Asn Ser Ala Met Ile His Leu Ile His Val Asp Pro Arg Leu 125 130 135His Thr Pro Met Tyr Phe Leu Leu Ser Gln Leu Ser Leu Met Asp 140 145 150Leu Met Tyr Ile Ser Thr Thr Val Pro Lys Met Ala Tyr Asn Phe 155 160 165Leu Ser Gly Gln Lys Gly Ile Ser Phe Leu Gly Cys Gly Val Gln 170 175 180Ser Phe Phe Phe Leu Thr Met Ala Cys Ser Glu Gly Leu Leu Leu 185 190 195Thr Ser Met Ala Tyr Asp Arg Tyr Leu Ala Ile Cys His Ser Leu 200 205 210Tyr Tyr Pro Ile Arg Met Ser Lys Met Met Cys Val Lys Met Ile 215 220 225Gly Gly Ser Trp Thr Leu Gly Ser Ile Asn Ser Leu Ala His Thr 230 235 240Val Phe Ala Leu His Ile Pro Tyr Cys Arg Ser Arg Ala Ile Asp 245 250 255His Phe Phe Cys Asp Val Pro Ala Met Leu Leu Leu Ala Cys Thr 260 265 270Asp Thr Trp Val Tyr Glu Tyr Met Val Phe Val Ser Thr Ser Leu 275 280 285Phe Leu Leu Phe Pro Phe Ile Gly Ile Thr Ser Ser Cys Gly Arg 290 295 300Val Leu Phe Ala Val Tyr His Met His Ser Lys Glu Gly Arg Lys 305 310 315Lys Ala Phe Thr Thr Ile Ser Thr His Leu Thr Val Val Ile Phe 320 325 330Tyr Tyr Ala Pro Phe Val Tyr Thr Tyr Leu Arg Pro Arg Asn Leu 335 340 345Arg Ser Pro Ala Glu Asp Lys Ile Leu Ala Val Phe Tyr Thr Ile 350 355 360Leu Thr Pro Met Leu Asn Pro Ile Ile Tyr Ser Leu Arg Asn Lys 365 370 375Glu Val Leu Gly Ala Met Arg Arg Val Phe Gly Ile Phe Ser Phe 380 385 390Leu Lys Glu 37 314 PRT Homo sapiens misc_feature Incyte ID No 7476809CD137 Met Glu Arg Gln Asn Gln Ser Cys Val Val Glu Phe Ile Leu Leu 1 5 10 15Gly Phe Ser Asn Tyr Pro Glu Leu Gln Gly Gln Leu Phe Val Ala 20 25 30 PheLeu Val Ile Tyr Leu Val Thr Leu Ile Gly Asn Ala Ile Ile 35 40 45 Ile ValIle Val Ser Leu Asp Gln Ser Leu His Val Pro Met Tyr 50 55 60 Leu Phe LeuLeu Asn Leu Ser Val Val Asp Leu Ser Phe Ser Ala 65 70 75 Val Ile Met ProGlu Met Leu Val Val Leu Ser Thr Glu Lys Thr 80 85 90 Thr Ile Ser Phe GlyGly Cys Phe Ala Gln Met Tyr Phe Ile Leu 95 100 105 Leu Phe Gly Gly AlaGlu Cys Phe Leu Leu Gly Ala Met Ala Tyr 110 115 120 Asp Arg Phe Ala AlaIle Cys His Pro Leu Asn Tyr Gln Met Ile 125 130 135 Met Asn Lys Gly ValPhe Met Lys Leu Ile Ile Phe Ser Trp Ala 140 145 150 Leu Gly Phe Met LeuGly Thr Val Gln Thr Ser Trp Val Ser Ser 155 160 165 Phe Pro Phe Cys GlyLeu Asn Glu Ile Asn His Ile Ser Cys Glu 170 175 180 Thr Pro Ala Val LeuGlu Leu Ala Cys Ala Asp Thr Phe Leu Phe 185 190 195 Glu Ile Tyr Ala PheThr Gly Thr Phe Leu Ile Ile Leu Val Pro 200 205 210 Phe Leu Leu Ile LeuLeu Ser Tyr Ile Arg Val Leu Phe Ala Ile 215 220 225 Leu Lys Met Pro SerThr Thr Gly Arg Gln Lys Ala Phe Ser Thr 230 235 240 Cys Ala Ala His LeuThr Ser Val Thr Leu Phe Tyr Gly Thr Ala 245 250 255 Ser Met Thr Tyr LeuGln Pro Lys Ser Gly Tyr Ser Pro Glu Thr 260 265 270 Lys Lys Val Met SerLeu Ser Tyr Ser Leu Leu Thr Pro Leu Leu 275 280 285 Asn Leu Leu Ile TyrSer Leu Arg Asn Ser Glu Met Lys Arg Ala 290 295 300 Leu Met Lys Leu TrpArg Arg Arg Val Val Leu His Thr Ile 305 310 38 327 PRT Homo sapiensmisc_feature Incyte ID No 7476048CD1 38 Met Ala Ile Phe Asn Asn Thr ThrSer Ser Ser Ser Asn Phe Leu 1 5 10 15 Leu Thr Ala Phe Pro Gly Leu GluCys Ala His Val Trp Ile Ser 20 25 30 Ile Pro Val Cys Cys Leu Tyr Thr IleAla Leu Leu Gly Asn Ser 35 40 45 Met Ile Phe Leu Val Ile Ile Thr Lys ArgArg Leu His Lys Pro 50 55 60 Met Tyr Tyr Phe Leu Ser Met Leu Ala Ala ValAsp Leu Cys Leu 65 70 75 Thr Ile Thr Thr Leu Pro Thr Val Leu Gly Val LeuTrp Phe His 80 85 90 Ala Arg Glu Ile Ser Phe Lys Ala Cys Phe Ile Gln MetPhe Phe 95 100 105 Val His Ala Phe Ser Leu Leu Glu Ser Ser Val Leu ValAla Met 110 115 120 Ala Phe Asp Arg Phe Val Ala Ile Cys Asn Pro Leu AsnTyr Ala 125 130 135 Thr Ile Leu Thr Asp Arg Met Val Leu Val Ile Gly LeuVal Ile 140 145 150 Cys Ile Arg Pro Ala Val Phe Leu Leu Pro Leu Leu ValAla Ile 155 160 165 Asn Thr Val Ser Phe His Gly Gly His Glu Leu Ser HisPro Phe 170 175 180 Cys Tyr His Pro Glu Val Ile Lys Tyr Thr Tyr Ser LysPro Trp 185 190 195 Ile Ser Ser Phe Trp Gly Leu Phe Leu Gln Leu Tyr LeuAsn Gly 200 205 210 Thr Asp Val Leu Phe Ile Leu Phe Ser Tyr Val Leu IleLeu Arg 215 220 225 Thr Val Leu Gly Ile Val Ala Arg Lys Lys Gln Gln LysAla Leu 230 235 240 Ser Thr Cys Val Cys His Ile Cys Ala Val Thr Ile PheTyr Val 245 250 255 Pro Leu Ile Ser Leu Ser Leu Ala His Arg Leu Phe HisSer Thr 260 265 270 Pro Arg Val Leu Cys Ser Thr Leu Ala Asn Ile Tyr LeuLeu Leu 275 280 285 Pro Pro Val Leu Asn Pro Ile Ile Tyr Ser Leu Lys ThrLys Thr 290 295 300 Ile Arg Gln Ala Met Phe Gln Leu Leu Gln Ser Lys GlySer Trp 305 310 315 Gly Phe Asn Val Arg Gly Leu Arg Gly Arg Trp Asp 320325 39 319 PRT Homo sapiens misc_feature Incyte ID No 7476679CD1 39 MetGlu Ile Ala Asn Val Ser Ser Pro Glu Val Phe Val Leu Leu 1 5 10 15 GlyPhe Ser Thr Arg Pro Ser Leu Glu Thr Val Leu Phe Ile Val 20 25 30 Val LeuSer Phe Tyr Met Val Ser Ile Leu Gly Asn Gly Ile Ile 35 40 45 Ile Leu ValSer His Thr Asp Val His Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu AlaAsn Leu Pro Phe Leu Asp Met Ser Phe Thr Thr 65 70 75 Ser Ile Val Pro GlnLeu Leu Ala Asn Leu Trp Gly Pro Gln Lys 80 85 90 Thr Ile Ser Tyr Gly GlyCys Val Val Gln Phe Tyr Ile Ser His 95 100 105 Trp Leu Gly Ala Thr GluCys Val Leu Leu Ala Thr Met Ser Tyr 110 115 120 Asp Arg Tyr Ala Ala IleCys Arg Pro Leu His Tyr Thr Val Ile 125 130 135 Met His Pro Gln Leu CysLeu Gly Leu Ala Leu Ala Ser Trp Leu 140 145 150 Gly Gly Leu Thr Thr SerMet Val Gly Ser Thr Leu Thr Met Leu 155 160 165 Leu Pro Leu Cys Gly AsnAsn Cys Ile Asp His Phe Phe Cys Glu 170 175 180 Met Pro Leu Ile Met GlnLeu Ala Cys Val Asp Thr Ser Leu Asn 185 190 195 Glu Met Glu Met Tyr LeuAla Ser Phe Val Phe Val Val Leu Pro 200 205 210 Leu Gly Leu Ile Leu ValSer Tyr Gly His Ile Ala Arg Ala Val 215 220 225 Leu Lys Ile Arg Ser AlaGlu Gly Arg Arg Lys Ala Phe Asn Thr 230 235 240 Cys Ser Ser His Val AlaVal Val Ser Leu Phe Tyr Gly Ser Ile 245 250 255 Ile Phe Met Tyr Leu GlnPro Ala Lys Ser Thr Ser His Glu Gln 260 265 270 Gly Lys Phe Ile Ala LeuPhe Tyr Thr Val Val Thr Pro Ala Leu 275 280 285 Asn Pro Leu Ile Tyr ThrLeu Arg Asn Thr Glu Val Lys Ser Ala 290 295 300 Leu Arg His Met Val LeuGlu Asn Cys Cys Gly Ser Ala Gly Lys 305 310 315 Leu Ala Gln Ile 40 308PRT Homo sapiens misc_feature Incyte ID No 7486996CD1 40 Met Asp Thr GlyAsn Lys Thr Leu Pro Gln Asp Phe Leu Leu Leu 1 5 10 15 Gly Phe Pro GlySer Gln Thr Leu Gln Leu Ser Leu Phe Met Leu 20 25 30 Phe Leu Val Met TyrIle Leu Thr Val Ser Gly Asn Val Ala Ile 35 40 45 Leu Met Leu Val Ser ThrSer His Gln Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ser Asn Leu SerPhe Leu Glu Ile Trp Tyr Thr Thr 65 70 75 Ala Ala Val Pro Lys Ala Leu AlaIle Leu Leu Gly Arg Ser Gln 80 85 90 Thr Ile Ser Phe Thr Ser Cys Leu LeuGln Met Tyr Phe Val Phe 95 100 105 Ser Leu Gly Cys Thr Glu Tyr Phe LeuLeu Ala Ala Met Ala Tyr 110 115 120 Asp Arg Cys Leu Ala Ile Cys Tyr ProLeu His Tyr Gly Ala Ile 125 130 135 Met Ser Ser Leu Leu Ser Ala Gln LeuAla Leu Gly Ser Trp Val 140 145 150 Cys Gly Phe Val Ala Ile Ala Val ProThr Ala Leu Ile Ser Gly 155 160 165 Leu Ser Phe Cys Gly Pro Arg Ala IleAsn His Phe Phe Cys Asp 170 175 180 Ile Ala Pro Trp Ile Ala Leu Ala CysThr Asn Thr Gln Ala Val 185 190 195 Glu Leu Val Ala Phe Val Ile Ala ValVal Val Ile Leu Ser Ser 200 205 210 Cys Leu Ile Thr Phe Val Ser Tyr ValTyr Ile Ile Ser Thr Ile 215 220 225 Leu Arg Ile Pro Ser Ala Ser Gly ArgSer Lys Ala Phe Ser Thr 230 235 240 Cys Ser Ser His Leu Thr Val Val LeuIle Trp Tyr Gly Ser Thr 245 250 255 Val Phe Leu His Val Arg Thr Ser IleLys Asp Ala Leu Asp Leu 260 265 270 Ile Lys Ala Val His Val Leu Asn ThrVal Val Thr Pro Val Leu 275 280 285 Asn Pro Phe Ile Tyr Thr Leu Arg AsnLys Glu Val Arg Glu Thr 290 295 300 Leu Leu Lys Lys Trp Lys Gly Lys 30541 310 PRT Homo sapiens misc_feature Incyte ID No 7490489CD1 41 Met GluSer Asn Gln Thr Trp Ile Thr Glu Val Ile Leu Leu Gly 1 5 10 15 Phe GlnVal Asp Pro Ala Leu Glu Leu Phe Leu Phe Gly Phe Phe 20 25 30 Leu Leu PheTyr Ser Leu Thr Leu Met Gly Asn Gly Ile Ile Leu 35 40 45 Gly Leu Ile TyrLeu Asp Ser Arg Leu His Thr Pro Met Tyr Val 50 55 60 Phe Leu Ser His LeuAla Ile Val Asp Met Ser Tyr Ala Ser Ser 65 70 75 Thr Val Pro Lys Met LeuAla Asn Leu Val Met His Lys Lys Val 80 85 90 Ile Ser Phe Ala Pro Cys IleLeu Gln Thr Phe Leu Tyr Leu Ala 95 100 105 Phe Ala Ile Thr Glu Cys LeuIle Leu Val Met Met Cys Tyr Asp 110 115 120 Arg Tyr Val Ala Ile Cys HisPro Leu Gln Tyr Thr Leu Ile Met 125 130 135 Asn Trp Arg Val Cys Thr ValLeu Ala Ser Thr Cys Trp Ile Phe 140 145 150 Ser Phe Leu Leu Ala Leu ValHis Ile Thr Leu Ile Leu Arg Leu 155 160 165 Pro Phe Cys Gly Pro Gln LysIle Asn His Phe Phe Cys Gln Ile 170 175 180 Met Ser Val Phe Lys Leu AlaCys Ala Asp Thr Arg Leu Asn Gln 185 190 195 Val Val Leu Phe Ala Gly SerAla Phe Ile Leu Val Gly Pro Leu 200 205 210 Cys Leu Val Leu Val Ser TyrLeu His Ile Leu Val Ala Ile Leu 215 220 225 Arg Ile Gln Ser Gly Glu GlyArg Arg Lys Ala Phe Ser Thr Cys 230 235 240 Ser Ser His Leu Cys Val ValGly Leu Phe Phe Gly Ser Ala Ile 245 250 255 Val Met Tyr Met Ala Pro LysSer Ser His Ser Gln Glu Arg Arg 260 265 270 Lys Ile Leu Ser Leu Phe TyrSer Leu Phe Asn Pro Ile Leu Asn 275 280 285 Pro Leu Ile Tyr Ser Leu ArgAsn Ala Glu Val Lys Gly Ala Leu 290 295 300 Lys Arg Val Leu Trp Lys GlnArg Ser Met 305 310 42 312 PRT Homo sapiens misc_feature Incyte ID No7475304CD1 42 Met Glu Gln His Asn Leu Thr Thr Val Asn Glu Phe Ile LeuThr 1 5 10 15 Gly Ile Thr Asp Ile Ala Glu Leu Gln Ala Pro Leu Phe AlaLeu 20 25 30 Phe Leu Met Ile Tyr Val Ile Ser Val Met Gly Asn Leu Gly Met35 40 45 Ile Val Leu Thr Lys Leu Asp Ser Arg Leu Gln Thr Pro Met Tyr 5055 60 Phe Phe Leu Arg His Leu Ala Phe Met Asp Leu Gly Tyr Ser Thr 65 7075 Thr Val Gly Pro Lys Met Leu Val Asn Phe Val Val Asp Lys Asn 80 85 90Ile Ile Ser Tyr Tyr Phe Cys Ala Thr Gln Leu Ala Phe Phe Leu 95 100 105Val Phe Ile Gly Ser Glu Leu Phe Ile Leu Ser Ala Met Ser Tyr 110 115 120Asp Leu Tyr Val Ala Ile Cys Asn Pro Leu Leu Tyr Thr Val Ile 125 130 135Met Ser Arg Arg Val Cys Gln Val Leu Val Ala Ile Pro Tyr Leu 140 145 150Tyr Cys Thr Phe Ile Ser Leu Leu Val Thr Ile Lys Ile Phe Thr 155 160 165Leu Ser Phe Cys Gly Tyr Asn Val Ile Ser His Phe Tyr Cys Asp 170 175 180Ser Leu Pro Leu Leu Pro Leu Leu Cys Ser Asn Thr His Glu Ile 185 190 195Glu Leu Ile Ile Leu Ile Phe Ala Ala Ile Asp Leu Ile Ser Ser 200 205 210Leu Leu Ile Val Leu Leu Ser Tyr Leu Leu Ile Leu Val Ala Ile 215 220 225Leu Arg Met Asn Ser Ala Gly Arg Gln Lys Ala Phe Ser Thr Cys 230 235 240Gly Ala His Leu Thr Val Val Ile Val Phe Tyr Gly Thr Leu Leu 245 250 255Phe Met Tyr Val Gln Pro Lys Ser Ser His Ser Phe Asp Thr Asp 260 265 270Lys Val Ala Ser Ile Phe Tyr Thr Leu Val Ile Pro Met Leu Asn 275 280 285Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val Lys Tyr Ala Leu 290 295 300Arg Arg Thr Trp Asn Asn Leu Cys Asn Ile Phe Val 305 310 43 314 PRT Homosapiens misc_feature Incyte ID No 7475248CD1 43 Met Thr Arg Lys Asn TyrThr Ser Leu Thr Glu Phe Val Leu Leu 1 5 10 15 Gly Leu Ala Asp Thr LeuGlu Leu Gln Ile Ile Leu Phe Leu Phe 20 25 30 Phe Leu Val Ile Tyr Thr LeuThr Val Leu Gly Asn Leu Gly Met 35 40 45 Ile Leu Leu Ile Arg Ile Asp SerGln Leu His Thr Pro Met Tyr 50 55 60 Phe Phe Leu Ala Asn Leu Ser Phe ValAsp Val Cys Asn Ser Thr 65 70 75 Thr Ile Thr Pro Lys Met Leu Ala Asp LeuLeu Ser Glu Lys Lys 80 85 90 Thr Ile Ser Phe Ala Gly Cys Phe Leu Gln MetTyr Phe Phe Ile 95 100 105 Ser Leu Ala Thr Thr Glu Cys Ile Leu Phe GlyLeu Met Ala Tyr 110 115 120 Asp Arg Tyr Ala Ala Ile Cys Arg Pro Leu LeuTyr Ser Leu Ile 125 130 135 Met Ser Arg Thr Val Tyr Leu Lys Met Ala AlaGly Ala Phe Ala 140 145 150 Ala Gly Leu Leu Asn Phe Met Val Asn Thr SerHis Val Ser Ser 155 160 165 Leu Ser Phe Cys Asp Ser Asn Val Ile His HisPhe Phe Cys Asp 170 175 180 Ser Pro Pro Leu Phe Lys Leu Ser Cys Ser AspThr Ile Leu Lys 185 190 195 Glu Ser Ile Ser Ser Ile Leu Ala Gly Val AsnIle Val Gly Thr 200 205 210 Leu Leu Val Ile Leu Ser Ser Tyr Ser Tyr ValLeu Phe Ser Ile 215 220 225 Phe Ser Met His Ser Gly Glu Gly Arg His ArgAla Phe Ser Thr 230 235 240 Cys Ala Ser His Leu Thr Ala Ile Ile Leu PheTyr Ala Thr Cys 245 250 255 Ile Tyr Thr Tyr Leu Arg Pro Ser Ser Ser TyrSer Leu Asn Gln 260 265 270 Asp Lys Val Ala Ser Val Phe Tyr Thr Val ValIle Pro Met Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Ser Lys GluVal Lys Lys Ala 290 295 300 Leu Ala Asn Val Ile Ser Arg Lys Arg Thr SerSer Phe Leu 305 310 44 314 PRT Homo sapiens misc_feature Incyte ID No7475191CD1 44 Met Leu Met Asn Tyr Ser Ser Ala Thr Glu Phe Tyr Leu LeuGly 1 5 10 15 Phe Pro Gly Ser Glu Glu Leu His His Ile Leu Phe Ala IlePhe 20 25 30 Phe Phe Phe Tyr Leu Val Thr Leu Met Gly Asn Thr Val Ile Ile35 40 45 Met Ile Val Cys Val Asp Lys Arg Leu Gln Ser Pro Met Tyr Phe 5055 60 Phe Leu Gly His Leu Ser Ala Leu Glu Ile Leu Val Thr Thr Ile 65 7075 Ile Val Pro Val Met Leu Trp Gly Leu Leu Leu Pro Gly Met Gln 80 85 90Thr Ile Tyr Leu Ser Ala Cys Val Val Gln Leu Phe Leu Tyr Leu 95 100 105Ala Val Gly Thr Thr Glu Phe Ala Leu Leu Gly Ala Met Ala Val 110 115 120Asp Arg Tyr Val Ala Val Cys Asn Pro Leu Arg Tyr Asn Ile Ile 125 130 135Met Asn Arg His Thr Cys Asn Phe Val Val Leu Val Ser Trp Val 140 145 150Phe Gly Phe Leu Phe Gln Ile Trp Pro Val Tyr Val Met Phe Gln 155 160 165Leu Thr Tyr Cys Lys Ser Asn Val Val Asn Asn Phe Phe Cys Asp 170 175 180Arg Gly Gln Leu Leu Lys Leu Ser Cys Asn Asn Thr Leu Phe Thr 185 190 195Glu Phe Ile Leu Phe Leu Met Ala Val Phe Val Leu Phe Gly Ser 200 205 210Leu Ile Pro Thr Ile Val Ser Asn Ala Tyr Ile Ile Ser Thr Ile 215 220 225Leu Lys Ile Pro Ser Ser Ser Gly Arg Arg Lys Ser Phe Ser Thr 230 235 240Cys Ala Ser His Phe Thr Cys Val Val Ile Gly Tyr Gly Ser Cys 245 250 255Leu Phe Leu Tyr Val Lys Pro Lys Gln Thr Gln Ala Ala Asp Tyr 260 265 270Asn Trp Val Val Ser Leu Met Val Ser Val Val Thr Pro Phe Leu 275 280 285Asn Pro Phe Ile Phe Thr Leu Arg Asn Asp Lys Val Ile Glu Ala 290 295 300Leu Arg Asp Gly Val Lys Arg Cys Cys Gln Leu Phe Arg Asn 305 310 45 318PRT Homo sapiens misc_feature Incyte ID No 7480413CD1 45 Met Cys Ser GlyAsn Gln Thr Ser Gln Asn Gln Thr Ala Ser Thr 1 5 10 15 Asp Phe Thr LeuThr Gly Leu Phe Ala Glu Ser Lys His Ala Ala 20 25 30 Leu Leu Tyr Thr ValThr Phe Leu Leu Phe Leu Met Ala Leu Thr 35 40 45 Gly Asn Ala Leu Leu IleLeu Leu Ile His Ser Glu Pro Arg Leu 50 55 60 His Thr Pro Met Tyr Phe PheIle Ser Gln Leu Ala Leu Met Asp 65 70 75 Leu Met Tyr Leu Cys Val Thr ValPro Lys Met Leu Val Gly Gln 80 85 90 Val Thr Gly Asp Asp Thr Ile Ser ProSer Gly Cys Gly Ile Gln 95 100 105 Met Phe Phe His Leu Thr Leu Ala GlyAla Glu Val Phe Leu Leu 110 115 120 Ala Ala Met Ala Tyr Asp Arg Tyr AlaAla Val Cys Arg Pro Leu 125 130 135 His Tyr Pro Leu Leu Met Asn Gln ArgVal Cys Gln Leu Leu Val 140 145 150 Ser Ala Cys Trp Val Leu Gly Met ValAsp Gly Leu Leu Leu Thr 155 160 165 Pro Ile Thr Met Ser Phe Pro Phe CysGln Ser Arg Lys Ile Leu 170 175 180 Ser Phe Phe Cys Glu Thr Pro Ala LeuLeu Lys Leu Ser Cys Ser 185 190 195 Asp Val Ser Leu Tyr Lys Met Leu ThrTyr Leu Cys Cys Ile Leu 200 205 210 Met Leu Leu Thr Pro Ile Met Val IleSer Ser Ser Tyr Thr Leu 215 220 225 Ile Leu His Leu Ile His Arg Met AsnSer Ala Ala Gly Arg Arg 230 235 240 Lys Ala Leu Ala Thr Cys Ser Ser HisMet Ile Ile Val Leu Leu 245 250 255 Leu Phe Gly Ala Ser Phe Tyr Thr TyrMet Leu Arg Ser Ser Tyr 260 265 270 His Thr Ala Glu Gln Asp Met Met ValSer Ala Phe Tyr Thr Ile 275 280 285 Phe Thr Pro Val Leu Asn Pro Leu IleTyr Ser Leu Arg Asn Lys 290 295 300 Asp Val Thr Arg Ala Leu Arg Ser MetMet Gln Ser Arg Met Asn 305 310 315 Gln Glu Lys 46 314 PRT Homo sapiensmisc_feature Incyte ID No 7476165CD1 46 Met Asp Gln Ile Asn His Thr AsnVal Lys Glu Phe Phe Phe Leu 1 5 10 15 Glu Leu Thr Arg Ser Arg Glu LeuGlu Phe Phe Leu Phe Val Val 20 25 30 Phe Phe Ala Val Tyr Val Ala Thr ValLeu Gly Asn Ala Leu Ile 35 40 45 Val Val Thr Ile Thr Cys Glu Ser Arg LeuHis Thr Pro Met Tyr 50 55 60 Phe Leu Leu Arg Asn Lys Ser Val Leu Asp IleVal Phe Ser Ser 65 70 75 Ile Thr Val Pro Lys Phe Leu Val Asp Leu Leu SerAsp Arg Lys 80 85 90 Thr Ile Ser Tyr Asn Asp Cys Met Ala Gln Ile Phe PhePhe His 95 100 105 Phe Ala Gly Gly Ala Asp Ile Phe Phe Leu Ser Val MetAla Tyr 110 115 120 Asp Arg Tyr Leu Ala Ile Ala Lys Pro Leu His Tyr ValThr Met 125 130 135 Met Arg Lys Glu Val Trp Val Ala Leu Val Val Ala SerTrp Val 140 145 150 Ser Gly Gly Leu His Ser Ile Ile Gln Val Ile Leu MetLeu Pro 155 160 165 Phe Pro Phe Cys Gly Pro Asn Thr Leu Asp Ala Phe TyrCys Tyr 170 175 180 Val Leu Gln Val Val Lys Leu Ala Cys Thr Asp Thr PheAla Leu 185 190 195 Glu Leu Phe Met Ile Ser Asn Asn Gly Leu Val Thr LeuLeu Trp 200 205 210 Phe Leu Leu Leu Leu Gly Ser Tyr Thr Val Ile Leu ValMet Leu 215 220 225 Arg Ser His Ser Gly Glu Gly Arg Asn Lys Ala Leu SerThr Cys 230 235 240 Thr Ser His Met Leu Val Val Thr Leu His Phe Val ProCys Val 245 250 255 Tyr Ile Tyr Cys Arg Pro Phe Met Thr Leu Pro Met AspThr Thr 260 265 270 Ile Ser Ile Asn Asn Thr Val Ile Thr Pro Met Leu AsnPro Ile 275 280 285 Ile Tyr Ser Leu Arg Asn Gln Glu Met Lys Ser Ala MetGln Arg 290 295 300 Leu Gln Arg Arg Leu Gly Pro Ser Glu Ser Arg Lys TrpGly 305 310 47 313 PRT Homo sapiens misc_feature Incyte ID No 7478345CD147 Met Ala Gly Glu Asn His Thr Thr Leu Pro Glu Phe Leu Leu Leu 1 5 10 15Gly Phe Ser Asp Leu Lys Ala Leu Gln Gly Pro Leu Phe Trp Val 20 25 30 ValLeu Leu Val Tyr Leu Val Thr Leu Leu Gly Asn Ser Leu Ile 35 40 45 Ile LeuLeu Thr Gln Val Ser Pro Ala Leu His Ser Pro Met Tyr 50 55 60 Phe Phe LeuArg Gln Leu Ser Val Val Glu Leu Phe Tyr Thr Thr 65 70 75 Asp Ile Val ProArg Thr Leu Ala Asn Leu Gly Ser Pro His Pro 80 85 90 Gln Ala Ile Ser PheGln Gly Cys Ala Ala Gln Met Tyr Val Phe 95 100 105 Ile Val Leu Gly IleSer Glu Cys Cys Leu Leu Thr Ala Met Ala 110 115 120 Tyr Asp Arg Tyr ValAla Ile Cys Gln Pro Leu Arg Tyr Ser Thr 125 130 135 Leu Leu Ser Pro ArgAla Cys Met Ala Met Val Gly Thr Ser Trp 140 145 150 Leu Thr Gly Ile IleThr Ala Thr Thr His Ala Ser Leu Ile Phe 155 160 165 Ser Leu Pro Phe ArgSer His Pro Ile Ile Pro His Phe Leu Cys 170 175 180 Asp Ile Leu Pro ValLeu Arg Leu Ala Ser Ala Gly Lys His Arg 185 190 195 Ser Glu Ile Ser ValMet Thr Ala Thr Ile Val Phe Ile Met Ile 200 205 210 Pro Phe Ser Leu IleVal Thr Ser Tyr Ile Arg Ile Leu Gly Ala 215 220 225 Ile Leu Ala Met AlaSer Thr Gln Ser Arg Arg Lys Val Phe Ser 230 235 240 Thr Cys Ser Ser HisLeu Leu Val Val Ser Leu Phe Phe Gly Thr 245 250 255 Ala Ser Ile Thr TyrIle Arg Pro Gln Ala Gly Ser Ser Val Thr 260 265 270 Thr Asp Arg Val LeuSer Leu Phe Tyr Thr Val Ile Thr Pro Met 275 280 285 Leu Asn Pro Ile IleTyr Thr Leu Arg Asn Lys Asp Val Arg Arg 290 295 300 Ala Leu Arg His LeuVal Lys Arg Gln Arg Pro Ser Pro 305 310 48 311 PRT Homo sapiensmisc_feature Incyte ID No 7475245CD1 48 Met Gly Lys Glu Asn Cys Thr ThrVal Ala Glu Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser Asp Val Pro Glu LeuArg Val Cys Leu Phe Leu Leu 20 25 30 Phe Leu Leu Ile Tyr Gly Val Thr LeuLeu Ala Asn Leu Gly Met 35 40 45 Thr Ala Leu Ile Gln Val Ser Ser Arg LeuHis Thr Pro Val Tyr 50 55 60 Phe Phe Leu Ser His Leu Ser Phe Val Asp PheCys Tyr Ser Ser 65 70 75 Ile Ile Val Pro Lys Met Leu Ala Asn Ile Phe AsnLys Asp Lys 80 85 90 Ala Ile Ser Phe Leu Gly Cys Met Val Gln Phe Tyr LeuPhe Cys 95 100 105 Thr Cys Gly Val Thr Glu Val Phe Leu Leu Ala Val MetAla Tyr 110 115 120 Asp Arg Phe Val Ala Ile Cys Asn Pro Leu Leu Tyr MetVal Thr 125 130 135 Met Ser Gln Lys Leu Arg Val Glu Leu Thr Ser Cys CysTyr Phe 140 145 150 Cys Gly Thr Val Cys Ser Leu Ile His Ser Ser Leu AlaLeu Arg 155 160 165 Ile Leu Phe Tyr Arg Ser Asn Val Ile Asn His Phe PheCys Asp 170 175 180 Leu Pro Pro Leu Leu Ser Leu Ala Cys Ser Asp Val ThrVal Asn 185 190 195 Glu Thr Leu Leu Phe Leu Val Ala Thr Leu Asn Glu SerVal Thr 200 205 210 Ile Met Ile Ile Leu Thr Ser Tyr Leu Leu Ile Leu ThrThr Ile 215 220 225 Leu Lys Ile His Ser Ala Glu Ser Arg His Lys Ala PheSer Thr 230 235 240 Cys Ala Ser His Leu Thr Ala Ile Thr Val Ser His GlyThr Ile 245 250 255 Leu Tyr Ile Tyr Cys Arg Pro Ser Ser Gly Asn Ser GlyAsp Val 260 265 270 Asp Lys Val Ala Thr Val Phe Tyr Thr Val Val Ile ProMet Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys Asp Val AsnLys Ala 290 295 300 Leu Arg Lys Val Met Gly Ser Lys Ile His Ser 305 31049 310 PRT Homo sapiens misc_feature Incyte ID No 7485481CD1 49 Met ProAsn Phe Thr Asp Val Thr Glu Phe Thr Leu Leu Gly Leu 1 5 10 15 Thr CysArg Gln Glu Leu Gln Val Leu Phe Phe Val Val Phe Leu 20 25 30 Ala Val TyrMet Ile Thr Leu Leu Gly Asn Ile Gly Met Ile Ile 35 40 45 Leu Ile Ser IleSer Pro Gln Leu Gln Ser Pro Met Tyr Phe Phe 50 55 60 Leu Ser His Leu SerPhe Ala Asp Val Cys Phe Ser Ser Asn Val 65 70 75 Thr Pro Lys Met Leu GluAsn Leu Leu Ser Glu Thr Lys Thr Ile 80 85 90 Ser Tyr Val Gly Cys Leu ValGln Cys Tyr Phe Phe Ile Ala Val 95 100 105 Val His Val Glu Val Tyr IleLeu Ala Val Met Ala Phe Asp Arg 110 115 120 Tyr Met Ala Gly Cys Asn ProLeu Leu Tyr Gly Ser Lys Met Ser 125 130 135 Arg Thr Val Cys Val Arg LeuIle Ser Val Pro Tyr Val Tyr Gly 140 145 150 Phe Ser Val Ser Leu Ile CysThr Leu Trp Thr Tyr Gly Leu Tyr 155 160 165 Phe Cys Gly Asn Phe Glu IleAsn His Phe Tyr Cys Ala Asp Pro 170 175 180 Pro Leu Ile Gln Ile Ala CysGly Arg Val His Ile Lys Glu Ile 185 190 195 Thr Met Ile Val Ile Ala GlyIle Asn Phe Thr Tyr Ser Leu Ser 200 205 210 Val Val Leu Ile Ser Tyr ThrLeu Ile Val Val Ala Val Leu Arg 215 220 225 Met Arg Ser Ala Asp Gly ArgArg Lys Ala Phe Ser Thr Cys Gly 230 235 240 Ser His Leu Thr Ala Val SerMet Phe Tyr Gly Thr Pro Ile Phe 245 250 255 Met Tyr Leu Arg Arg Pro ThrGlu Glu Ser Val Glu Gln Gly Lys 260 265 270 Met Val Ala Val Phe Tyr ThrThr Val Ile Pro Met Leu Asn Pro 275 280 285 Met Ile Tyr Ser Leu Arg AsnLys Asp Val Lys Glu Ala Val Asn 290 295 300 Lys Ala Ile Thr Lys Thr TyrVal Arg Gln 305 310 50 331 PRT Homo sapiens misc_feature Incyte ID No7482835CD1 50 Met Leu Thr Pro Asn Asn Ala Cys Ser Val Pro Thr Ser PheArg 1 5 10 15 Leu Thr Gly Ile Pro Gly Leu Glu Ser Leu His Ile Trp LeuSer 20 25 30 Ile Pro Phe Gly Ser Met Tyr Leu Val Ala Val Leu Gly Asn Ile35 40 45 Thr Ile Leu Ala Val Val Arg Met Glu Tyr Ser Leu His Gln Pro 5055 60 Met Tyr Phe Phe Leu Cys Met Leu Ala Val Ile Asp Leu Val Leu 65 7075 Ser Thr Ser Thr Met Pro Lys Leu Leu Ala Ile Phe Trp Phe Gly 80 85 90Ala His Asn Ile Gly Val Asn Ala Cys Leu Ala Gln Met Phe Phe 95 100 105Ile His Cys Phe Ala Thr Val Glu Ser Gly Ile Phe Leu Ala Met 110 115 120Ala Phe Asp His Tyr Val Ala Ile Cys Asp Pro Leu His His Thr 125 130 135Leu Leu Leu Thr His Ala Val Val Gly Arg Leu Gly Leu Ala Ala 140 145 150Leu Leu Arg Gly Val Ile Tyr Ile Gly Pro Leu Pro Leu Val Ile 155 160 165Cys Leu Arg Leu Pro Leu Tyr His Thr Gln Ile Ile Ala His Ser 170 175 180Tyr Cys Glu His Met Ala Val Val Thr Leu Ala Cys Gly Val Thr 185 190 195Thr Arg Val Asn Asn Leu Tyr Gly Met Gly Ile Gly Phe Leu Val 200 205 210Leu Ile Leu Asp Ser Leu Ala Ile Thr Ala Ser Tyr Val Met Ile 215 220 225Phe Arg Ala Val Met Gly Leu Ala Thr Ser Glu Ala Arg Leu Lys 230 235 240Thr Leu Gly Thr Cys Gly Ser His Ile Cys Ala Ile Leu Val Phe 245 250 255Tyr Ile Pro Ile Ala Val Ser Ser Leu Thr His Arg Phe Gly His 260 265 270Arg Val Pro Pro His Ile His Ile His Ile His Ile His Ile His 275 280 285Ile His Ile His Ile His Ile Leu Leu Ala Asn Ile Tyr Leu Leu 290 295 300Ile Pro Pro Ile Leu Asn Pro Ile Val Tyr Ala Val His Thr Lys 305 310 315Gln Ile Arg Glu Ala Leu Leu His Ile Lys Ala Arg Thr Gln Thr 320 325 330Arg 51 312 PRT Homo sapiens misc_feature Incyte ID No 7475100CD1 51 MetAsp Glu Ala Asn His Ser Val Val Ser Glu Phe Val Phe Leu 1 5 10 15 GlyLeu Ser Asp Ser Arg Lys Ile Gln Leu Leu Leu Phe Leu Phe 20 25 30 Phe SerVal Phe Tyr Val Ser Ser Leu Met Gly Asn Leu Leu Ile 35 40 45 Val Leu ThrVal Thr Ser Asp Pro Arg Leu Gln Ser Pro Met Tyr 50 55 60 Phe Leu Leu AlaAsn Leu Ser Ile Ile Asn Leu Val Phe Cys Ser 65 70 75 Ser Thr Ala Pro LysMet Ile Tyr Asp Leu Phe Arg Lys His Lys 80 85 90 Thr Ile Ser Phe Gly GlyCys Val Val Gln Ile Phe Phe Ile His 95 100 105 Ala Val Gly Gly Thr GluMet Val Leu Leu Ile Ala Met Ala Phe 110 115 120 Asp Arg Tyr Val Ala IleCys Lys Pro Leu His Tyr Leu Thr Ile 125 130 135 Met Asn Pro Gln Arg CysIle Leu Phe Leu Val Ile Ser Trp Ile 140 145 150 Ile Gly Ile Ile His SerVal Ile Gln Leu Ala Phe Val Val Asp 155 160 165 Leu Leu Phe Cys Gly ProAsn Glu Leu Asp Ser Phe Phe Cys Asp 170 175 180 Leu Pro Arg Phe Ile LysLeu Ala Cys Ile Glu Thr Tyr Thr Leu 185 190 195 Gly Phe Met Val Thr AlaAsn Ser Gly Phe Ile Ser Leu Ala Ser 200 205 210 Phe Leu Ile Leu Ile IleSer Tyr Ile Phe Ile Leu Val Thr Val 215 220 225 Gln Lys Lys Ser Ser GlyGly Ile Phe Lys Ala Phe Ser Met Leu 230 235 240 Ser Ala His Val Ile ValVal Val Leu Val Phe Gly Pro Leu Ile 245 250 255 Phe Phe Tyr Ile Phe ProPhe Pro Thr Ser His Leu Asp Lys Phe 260 265 270 Leu Ala Ile Phe Asp AlaVal Ile Thr Pro Val Leu Asn Pro Val 275 280 285 Ile Tyr Thr Phe Arg AsnLys Glu Met Met Val Ala Met Arg Arg 290 295 300 Arg Cys Ser Gln Phe ValAsn Tyr Ser Lys Ile Phe 305 310 52 322 PRT Homo sapiens misc_featureIncyte ID No 7475185CD1 52 Met Asn Ser Leu Lys Asp Gly Asn His Thr AlaLeu Thr Gly Phe 1 5 10 15 Ile Leu Leu Gly Leu Thr Asp Asp Pro Ile LeuArg Val Ile Leu 20 25 30 Phe Met Ile Ile Leu Ser Gly Asn Leu Ser Ile IleIle Leu Ile 35 40 45 Arg Ile Ser Ser Gln Leu His His Pro Met Tyr Phe PheLeu Ser 50 55 60 His Leu Ala Phe Ala Asp Met Ala Tyr Ser Ser Ser Val ThrPro 65 70 75 Asn Met Leu Val Asn Phe Leu Val Glu Arg Asn Thr Val Ser Tyr80 85 90 Leu Gly Cys Ala Ile Gln Leu Gly Ser Ala Ala Phe Phe Ala Thr 95100 105 Val Glu Cys Val Leu Leu Ala Ala Met Ala Tyr Asp Arg Phe Val 110115 120 Ala Ile Cys Ser Pro Leu Leu Tyr Ser Thr Lys Met Ser Thr Gln 125130 135 Val Ser Val Gln Leu Leu Leu Val Val Tyr Ile Ala Gly Phe Leu 140145 150 Ile Ala Val Ser Tyr Thr Thr Ser Phe Tyr Phe Leu Leu Phe Cys 155160 165 Gly Pro Asn Gln Val Asn His Phe Phe Cys Asp Phe Ala Pro Leu 170175 180 Leu Glu Leu Ser Cys Ser Asp Ile Ser Val Ser Thr Val Val Leu 185190 195 Ser Phe Ser Ser Gly Ser Ile Ile Val Val Thr Val Cys Val Ile 200205 210 Ala Val Cys Tyr Ile Tyr Ile Leu Ile Thr Ile Leu Lys Met Arg 215220 225 Ser Thr Glu Gly His His Lys Ala Phe Ser Thr Cys Thr Ser His 230235 240 Leu Thr Val Val Thr Leu Phe Tyr Gly Thr Ile Thr Phe Ile Tyr 245250 255 Val Met Pro Asn Phe Ser Tyr Ser Thr Asp Gln Asn Lys Val Val 260265 270 Ser Val Leu Tyr Thr Val Val Ile Pro Met Leu Asn Pro Leu Ile 275280 285 Tyr Ser Leu Arg Asn Lys Glu Ile Lys Gly Ala Leu Lys Arg Glu 290295 300 Leu Val Arg Lys Ile Leu Ser His Asp Ala Cys Tyr Phe Ser Arg 305310 315 Thr Ser Asn Asn Asp Ile Thr 320 53 314 PRT Homo sapiensmisc_feature Incyte ID No 7477369CD1 53 Met Asp Val Gly Asn Lys Ser ThrMet Ser Glu Phe Val Leu Leu 1 5 10 15 Gly Leu Ser Asn Ser Trp Glu LeuGln Met Phe Phe Phe Met Val 20 25 30 Phe Ser Leu Leu Tyr Val Ala Thr MetVal Gly Asn Ser Leu Ile 35 40 45 Val Ile Thr Val Ile Val Asp Pro His LeuHis Ser Pro Met Tyr 50 55 60 Phe Leu Leu Thr Asn Leu Ser Ile Ile Asp MetSer Leu Ala Ser 65 70 75 Phe Ala Thr Pro Lys Met Ile Thr Asp Tyr Leu ThrGly His Lys 80 85 90 Thr Ile Ser Phe Asp Gly Cys Leu Thr Gln Ile Phe PheLeu His 95 100 105 Leu Phe Thr Gly Thr Glu Ile Ile Leu Leu Met Ala MetSer Phe 110 115 120 Asp Arg Tyr Ile Ala Ile Cys Lys Pro Leu His Tyr AlaSer Val 125 130 135 Ile Ser Pro Gln Val Cys Val Ala Leu Val Val Ala SerTrp Ile 140 145 150 Met Gly Val Met His Ser Met Ser Gln Val Ile Phe AlaLeu Thr 155 160 165 Leu Pro Phe Cys Gly Pro Tyr Glu Val Asp Ser Phe PheCys Asp 170 175 180 Leu Pro Val Val Phe Gln Leu Ala Cys Val Asp Thr TyrVal Leu 185 190 195 Gly Leu Phe Met Ile Ser Thr Ser Gly Ile Ile Ala LeuSer Cys 200 205 210 Phe Ile Val Leu Phe Asn Ser Tyr Val Ile Val Leu ValThr Val 215 220 225 Lys His His Ser Ser Arg Gly Ser Ser Lys Ala Leu SerThr Cys 230 235 240 Thr Ala His Phe Ile Val Val Phe Leu Phe Phe Gly ProCys Ile 245 250 255 Phe Ile Tyr Met Trp Pro Leu Ser Ser Phe Leu Thr AspLys Ile 260 265 270 Leu Ser Val Phe Tyr Thr Ile Phe Thr Pro Thr Leu AsnPro Ile 275 280 285 Ile Tyr Thr Leu Arg Asn Gln Glu Val Lys Ile Ala MetArg Lys 290 295 300 Leu Lys Asn Arg Phe Leu Asn Phe Asn Lys Ala Met ProSer 305 310 54 315 PRT Homo sapiens misc_feature Incyte ID No 7495138CD154 Met Arg Gln Asn Asn Asn Ile Thr Glu Phe Val Leu Leu Gly Phe 1 5 10 15Ser Gln Asp Pro Gly Val Gln Lys Ala Leu Phe Val Met Phe Leu 20 25 30 LeuThr Tyr Leu Val Thr Val Val Gly Asn Leu Leu Ile Val Val 35 40 45 Asp IleIle Ala Ser Pro Ser Leu Gly Ser Pro Met Tyr Phe Phe 50 55 60 Leu Ala CysLeu Ser Phe Ile Asp Ala Ala Tyr Ser Thr Thr Ile 65 70 75 Ser Pro Lys LeuIle Val Gly Leu Phe Cys Asp Lys Lys Thr Ile 80 85 90 Ser Phe Gln Gly CysMet Gly Gln Leu Phe Ile Asp His Phe Phe 95 100 105 Gly Gly Ala Glu ValPhe Leu Leu Val Val Met Ala Cys Asp Arg 110 115 120 Tyr Val Ala Ile CysLys Pro Leu His Tyr Leu Thr Ile Met Asn 125 130 135 Arg Gln Val Cys PheLeu Leu Leu Val Val Ala Met Ile Gly Gly 140 145 150 Phe Val His Ser AlaPhe Gln Ile Val Val Tyr Ser Leu Pro Phe 155 160 165 Cys Gly Pro Asn ValIle Val His Phe Ser Cys Asp Met His Pro 170 175 180 Leu Leu Glu Leu AlaCys Thr Asp Thr Tyr Phe Ile Gly Leu Thr 185 190 195 Val Val Val Asn SerGly Ala Ile Cys Met Val Ile Phe Asn Leu 200 205 210 Leu Leu Ile Ser TyrGly Val Ile Leu Ser Ser Leu Lys Thr Tyr 215 220 225 Ser Gln Glu Lys ArgGly Lys Ala Leu Ser Thr Cys Ser Ser Gly 230 235 240 Ser Thr Val Val ValLeu Phe Phe Val Pro Cys Ile Phe Ile Tyr 245 250 255 Val Arg Pro Val SerAsn Phe Pro Thr Asp Lys Phe Met Thr Val 260 265 270 Phe Tyr Thr Ile IleThr His Met Leu Ser Pro Leu Ile Tyr Thr 275 280 285 Leu Arg Asn Ser GluMet Arg Asn Ala Ile Glu Lys Leu Leu Gly 290 295 300 Lys Lys Leu Thr IlePhe Ile Ile Gly Gly Val Ser Val Leu Met 305 310 315 55 324 PRT Homosapiens misc_feature Incyte ID No 7475830CD1 55 Met Ala Glu Val Asn IleIle Tyr Val Thr Val Phe Ile Leu Lys 1 5 10 15 Gly Ile Thr Asn Arg ProGlu Leu Gln Ala Pro Cys Phe Gly Val 20 25 30 Phe Leu Val Ile Tyr Leu ValThr Val Leu Gly Asn Leu Gly Leu 35 40 45 Ile Thr Leu Ile Lys Ile Asp ThrArg Leu His Thr Pro Met Tyr 50 55 60 Tyr Phe Leu Ser His Leu Ala Phe ValAsp Leu Cys Tyr Ser Ser 65 70 75 Ala Ile Thr Pro Lys Met Met Val Asn PheVal Val Glu Arg Asn 80 85 90 Thr Ile Pro Phe His Ala Cys Ala Thr Gln LeuGly Cys Phe Leu 95 100 105 Thr Phe Met Ile Thr Glu Cys Phe Leu Leu AlaSer Met Ala Tyr 110 115 120 Asp Cys Tyr Val Ala Ile Cys Ser Pro Leu HisTyr Ser Thr Leu 125 130 135 Met Ser Arg Arg Val Cys Ile Gln Leu Val AlaVal Pro Tyr Ile 140 145 150 Tyr Ser Phe Leu Val Ala Leu Phe His Thr ValIle Thr Phe Arg 155 160 165 Leu Thr Tyr Cys Gly Pro Asn Leu Ile Asn HisPhe Tyr Cys Asp 170 175 180 Asp Leu Pro Phe Leu Ala Leu Ser Cys Ser AspThr His Met Lys 185 190 195 Glu Ile Leu Ile Phe Ala Phe Ala Gly Phe AspMet Ile Ser Ser 200 205 210 Ser Ser Ile Val Leu Thr Ser Tyr Ile Phe IleIle Ala Ala Ile 215 220 225 Leu Arg Ile Arg Ser Thr Gln Gly Gln His LysAla Ile Ser Thr 230 235 240 Cys Gly Ser His Met Val Thr Val Thr Ile PheTyr Gly Thr Leu 245 250 255 Ile Phe Met Tyr Leu Gln Pro Lys Ser Asn HisSer Leu Asp Thr 260 265 270 Asp Lys Met Ala Ser Val Phe Tyr Thr Val ValIle Pro Met Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Lys GluVal Lys Asp Ala 290 295 300 Ser Lys Lys Ala Leu Asp Lys Gly Cys Glu AsnLeu Gln Ile Leu 305 310 315 Thr Phe Leu Lys Ile Arg Lys Leu Tyr 320 56305 PRT Homo sapiens misc_feature Incyte ID No 7476161CD1 56 Met Gln ArgSer Asn His Thr Val Thr Glu Phe Ile Leu Leu Gly 1 5 10 15 Phe Thr ThrAsp Pro Gly Met Gln Leu Gly Leu Phe Val Val Phe 20 25 30 Leu Gly Val TyrSer Leu Thr Val Val Gly Asn Ser Thr Leu Ile 35 40 45 Val Leu Ile Cys AsnAsp Ser Cys Leu His Thr Pro Met Tyr Phe 50 55 60 Phe Thr Gly Asn Leu SerPhe Leu Asp Leu Trp Tyr Ser Ser Val 65 70 75 Tyr Thr Pro Lys Ile Leu ValThr Cys Ile Ser Glu Asp Lys Ser 80 85 90 Ile Ser Phe Ala Gly Cys Leu CysGln Phe Phe Phe Ser Ala Gly 95 100 105 Leu Ala Tyr Ser Glu Cys Tyr LeuLeu Ala Ala Val Ala Tyr Asp 110 115 120 Arg Tyr Val Ala Ile Ser Lys ProLeu Leu Tyr Ala Gln Ala Met 125 130 135 Ser Ile Lys Leu Cys Ala Leu LeuVal Ala Val Ser Tyr Cys Gly 140 145 150 Gly Phe Ile Asn Ser Ser Ile IleThr Lys Lys Thr Phe Ser Phe 155 160 165 Asn Phe Cys Arg Glu Asn Ile IleAsp Asp Phe Phe Cys Asp Leu 170 175 180 Leu Pro Leu Val Glu Leu Ala CysGly Glu Lys Gly Gly Tyr Lys 185 190 195 Ile Met Met Tyr Phe Leu Leu AlaSer Asn Val Ile Cys Pro Ala 200 205 210 Val Leu Ile Leu Ala Ser Tyr LeuPhe Ile Ile Thr Ser Val Leu 215 220 225 Arg Ile Ser Ser Ser Lys Gly TyrLeu Lys Ala Phe Ser Thr Cys 230 235 240 Ser Ser His Leu Thr Ser Val ThrLeu Tyr Tyr Gly Ser Ile Leu 245 250 255 Tyr Ile Tyr Ala Leu Pro Arg SerSer Tyr Ser Phe Asp Met Asp 260 265 270 Lys Ile Val Ser Thr Phe Tyr ThrVal Val Phe Pro Met Leu Asn 275 280 285 Leu Met Ile Tyr Ser Leu Arg AsnLys Asp Val Lys Glu Ala Leu 290 295 300 Lys Lys Leu Leu Pro 305 57 313PRT Homo sapiens misc_feature Incyte ID No 7475235CD1 57 Met Ser Ile IleAsn Thr Ser Tyr Val Glu Ile Thr Thr Phe Phe 1 5 10 15 Leu Val Gly MetPro Gly Leu Glu Tyr Ala His Ile Trp Ile Ser 20 25 30 Ile Pro Ile Cys SerMet Tyr Leu Ile Ala Ile Leu Gly Asn Gly 35 40 45 Thr Ile Leu Phe Ile IleLys Thr Glu Pro Ser Leu His Gly Pro 50 55 60 Met Tyr Tyr Phe Leu Ser MetLeu Ala Met Ser Asp Leu Gly Leu 65 70 75 Ser Leu Ser Ser Leu Pro Thr ValLeu Ser Ile Phe Leu Phe Asn 80 85 90 Ala Pro Glu Thr Ser Ser Ser Ala CysPhe Ala Gln Glu Phe Phe 95 100 105 Ile His Gly Phe Ser Val Leu Glu SerSer Val Leu Leu Ile Met 110 115 120 Ser Phe Asp Arg Phe Leu Ala Ile HisAsn Pro Leu Arg Tyr Thr 125 130 135 Ser Ile Leu Thr Thr Val Arg Val AlaGln Ile Gly Ile Val Phe 140 145 150 Ser Phe Lys Ser Met Leu Leu Val LeuPro Phe Pro Phe Thr Leu 155 160 165 Arg Ser Leu Arg Tyr Cys Lys Lys AsnGln Leu Ser His Ser Tyr 170 175 180 Cys Leu His Gln Asp Val Met Lys LeuAla Cys Ser Asp Asn Arg 185 190 195 Ile Asp Val Ile Tyr Gly Phe Phe GlyAla Leu Cys Leu Met Val 200 205 210 Asp Phe Ile Leu Ile Ala Val Ser TyrThr Leu Ile Leu Lys Thr 215 220 225 Val Pro Gly Ile Ala Ser Lys Lys GluGlu Leu Lys Ala Leu Asn 230 235 240 Thr Cys Val Ser His Ile Cys Ala ValIle Ile Phe Tyr Leu Pro 245 250 255 Ile Ile Asn Leu Ala Val Val His ArgPhe Ala Gly His Val Ser 260 265 270 Pro Leu Ile Asn Val Leu Met Ala AsnVal Leu Leu Leu Val Pro 275 280 285 Pro Leu Met Lys Pro Ile Val Tyr CysVal Lys Thr Lys Gln Ile 290 295 300 Arg Val Arg Val Val Ala Lys Leu CysGln Trp Lys Ile 305 310 58 305 PRT Homo sapiens misc_feature Incyte IDNo 7476246CD1 58 Met Leu Ser Phe Lys Asn Thr Phe Asn Cys Gln Ala Ser IleArg 1 5 10 15 Ile Ser Ala Asn Ile Phe His Leu Leu Phe His Ile Phe ThrPhe 20 25 30 Phe Gln Asp His Arg Pro Lys Thr His Asp Leu Val Thr Cys His35 40 45 Leu Ala Phe Val His Leu Val Met Leu Phe Thr Ala Met Glu Phe 5055 60 Leu Ser Pro Asp Met Phe Glu Ser Leu Asn Phe Gln Asn Asn Phe 65 7075 Arg Cys Lys Ala Phe Phe Tyr Leu His Lys Val Met Arg Gly Leu 80 85 90Ser Ile Cys Thr Thr Cys Leu Leu Ser Met Leu Gln Ala Ile Thr 95 100 105Ile Ser Leu Ser Thr Ser Trp Leu Val Arg Phe Lys His Lys Phe 110 115 120Thr Lys Tyr Asp Ile Leu Gly Leu Phe Val Phe Trp Phe Ser Asn 125 130 135Leu Ser Phe Ser Ser Asp Met Ile Ile Tyr Thr Val Gly Tyr Ser 140 145 150Asn Asp Pro Asp Asn Leu Asn Ile Ser Lys Tyr Cys Thr Phe Phe 155 160 165Pro Met Asn Val Leu Ile Arg Thr Leu Phe Leu Met Leu Ser Leu 170 175 180Ser Arg Asp Ala Phe Phe Ile Gly Ile Thr Leu Leu Ser Ser Val 185 190 195Tyr Met Val Ile Leu Leu Ser Arg His Gln Arg His Ser Gln His 200 205 210Phe His Ser Ser Ser Leu Ile Leu Arg Thr Ser Leu Val Lys Met 215 220 225Ala Thr Lys Thr Ile Leu Met Leu Val Asn Ser Phe Val Leu Met 230 235 240Tyr Ser Val Asp Phe Ile Leu Ser Ser Ser Thr Met Leu Leu Trp 245 250 255Val Ile Gly Pro Val Thr Tyr Gly Val His Lys Phe Val Val Asn 260 265 270Ala Tyr Ala Thr Val Ser Pro Leu Val Leu Ile Arg Ser Asp Lys 275 280 285Arg Ile Ile Asn Ile Leu Gln Lys Phe Gln Trp Lys Cys His Leu 290 295 300Phe Leu Thr Ser Trp 305 59 315 PRT Homo sapiens misc_feature Incyte IDNo 7474899CD1 59 Met Thr Thr His Arg Asn Asp Thr Leu Ser Thr Glu Ala SerAsp 1 5 10 15 Phe Leu Leu Asn Cys Phe Val Arg Ser Pro Ser Trp Gln HisTrp 20 25 30 Leu Ser Leu Pro Leu Ser Leu Leu Phe Leu Leu Ala Val Gly Ala35 40 45 Asn Thr Thr Leu Leu Met Thr Ile Trp Leu Glu Ala Ser Leu His 5055 60 Gln Pro Leu Tyr Tyr Leu Leu Ser Leu Leu Ser Leu Leu Asp Ile 65 7075 Val Leu Cys Leu Thr Val Ile Pro Lys Val Leu Thr Ile Phe Trp 80 85 90Phe Asp Leu Arg Pro Ile Ser Phe Pro Ala Cys Phe Leu Gln Met 95 100 105Tyr Ile Met Asn Cys Phe Leu Ala Met Glu Ser Cys Thr Phe Met 110 115 120Val Met Ala Tyr Asp Arg Tyr Val Ala Ile Cys His Pro Leu Arg 125 130 135Tyr Pro Ser Ile Ile Thr Asp His Phe Val Val Lys Ala Ala Met 140 145 150Phe Ile Leu Thr Arg Asn Val Leu Met Thr Leu Pro Ile Pro Ile 155 160 165Leu Ser Ala Gln Leu Arg Tyr Cys Gly Arg Asn Val Ile Glu Asn 170 175 180Cys Ile Cys Ala Asn Met Ser Val Ser Arg Leu Ser Cys Asp Asp 185 190 195Val Thr Ile Asn His Leu Tyr Gln Phe Ala Gly Gly Trp Thr Leu 200 205 210Leu Gly Ser Asp Leu Ile Leu Ile Phe Leu Ser Tyr Thr Phe Ile 215 220 225Leu Arg Ala Val Leu Arg Leu Lys Ala Glu Gly Ala Val Ala Lys 230 235 240Ala Leu Ser Thr Cys Gly Ser His Phe Met Leu Ile Leu Phe Phe 245 250 255Ser Thr Ile Leu Leu Val Phe Val Leu Thr His Val Ala Lys Lys 260 265 270Lys Val Ser Pro Asp Val Pro Val Leu Leu Asn Val Leu His His 275 280 285Val Ile Pro Ala Ala Leu Asn Pro Ile Ile Tyr Gly Val Arg Thr 290 295 300Gln Glu Ile Lys Gln Gly Met Gln Arg Leu Leu Lys Lys Gly Cys 305 310 31560 324 PRT Homo sapiens misc_feature Incyte ID No 7478353CD1 60 Met AlaVal Gly Arg Asn Asn Thr Ile Val Thr Lys Phe Ile Leu 1 5 10 15 Leu GlyLeu Ser Asp His Pro Gln Met Lys Ile Phe Leu Phe Met 20 25 30 Leu Phe LeuGly Leu Tyr Leu Leu Thr Leu Ala Trp Asn Leu Ser 35 40 45 Leu Ile Ala LeuIle Lys Met Asp Ser His Leu His Met Pro Met 50 55 60 Tyr Phe Phe Leu SerAsn Leu Ser Phe Leu Asp Ile Cys Tyr Val 65 70 75 Ser Ser Thr Ala Pro LysMet Leu Ser Asp Ile Ile Thr Glu Gln 80 85 90 Lys Thr Ile Ser Phe Val GlyCys Ala Thr Gln Tyr Phe Val Phe 95 100 105 Cys Gly Met Gly Leu Thr GluCys Phe Leu Leu Ala Ala Met Ala 110 115 120 Tyr Asp Arg Tyr Ala Ala IleCys Asn Pro Leu Leu Tyr Thr Val 125 130 135 Leu Ile Ser His Thr Leu CysLeu Lys Met Val Val Gly Ala Tyr 140 145 150 Val Gly Gly Phe Leu Ser SerPhe Ile Glu Thr Tyr Ser Val Tyr 155 160 165 Gln His Asp Phe Cys Gly ProTyr Met Ile Asn His Phe Phe Cys 170 175 180 Asp Leu Pro Pro Val Leu AlaLeu Ser Cys Ser Asp Thr Phe Thr 185 190 195 Ser Glu Val Val Thr Phe IleVal Ser Val Val Val Gly Ile Val 200 205 210 Ser Val Leu Val Val Leu IleSer Tyr Gly Tyr Ile Val Ala Ala 215 220 225 Val Val Lys Ile Ser Ser AlaThr Gly Arg Thr Lys Ala Phe Ser 230 235 240 Thr Cys Ala Ser His Leu ThrAla Val Thr Leu Phe Tyr Gly Ser 245 250 255 Gly Phe Phe Met Tyr Met ArgPro Ser Ser Ser Tyr Ser Leu Asn 260 265 270 Arg Asp Lys Val Val Ser IlePhe Tyr Ala Leu Val Ile Pro Val 275 280 285 Val Asn Pro Ile Ile Tyr SerPhe Arg Asn Lys Glu Ile Lys Asn 290 295 300 Ala Met Arg Lys Ala Met GluArg Asp Pro Gly Ile Ser His Gly 305 310 315 Gly Pro Phe Ile Phe Met ThrLeu Gly 320 61 314 PRT Homo sapiens misc_feature Incyte ID No 7473910CD161 Met Met Met Val Leu Arg Asn Leu Ser Met Glu Pro Thr Phe Ala 1 5 10 15Leu Leu Gly Phe Thr Asp Tyr Pro Lys Leu Gln Ile Pro Leu Phe 20 25 30 LeuVal Phe Leu Leu Met Tyr Val Ile Thr Val Val Gly Asn Leu 35 40 45 Gly MetIle Ile Ile Ile Lys Ile Asn Pro Lys Phe His Thr Pro 50 55 60 Met Tyr PhePhe Leu Ser His Leu Ser Phe Val Asp Phe Cys Tyr 65 70 75 Ser Ser Ile ValThr Pro Lys Leu Leu Glu Asn Leu Val Met Ala 80 85 90 Asp Lys Ser Ile PheTyr Phe Ser Cys Met Met Gln Tyr Phe Leu 95 100 105 Ser Cys Thr Ala ValVal Thr Glu Ser Phe Leu Leu Ala Val Met 110 115 120 Ala Tyr Asp Arg PheVal Ala Ile Cys Asn Pro Leu Leu Tyr Thr 125 130 135 Val Ala Met Ser GlnArg Leu Cys Ala Leu Leu Val Ala Gly Ser 140 145 150 Tyr Leu Trp Gly MetPhe Gly Pro Leu Val Leu Leu Cys Tyr Ala 155 160 165 Leu Arg Leu Asn PheSer Gly Pro Asn Val Ile Asn His Phe Phe 170 175 180 Cys Glu Tyr Thr AlaLeu Ile Ser Val Ser Gly Ser Asp Ile Leu 185 190 195 Ile Pro His Leu LeuLeu Phe Ser Phe Ala Thr Phe Asn Glu Met 200 205 210 Cys Thr Leu Leu IleIle Leu Thr Ser Tyr Val Phe Ile Phe Val 215 220 225 Thr Val Leu Lys IleArg Ser Val Ser Gly Arg His Lys Ala Phe 230 235 240 Ser Thr Trp Ala SerHis Leu Thr Ser Ile Thr Ile Phe His Gly 245 250 255 Thr Ile Leu Phe LeuTyr Cys Val Pro Asn Ser Lys Asn Ser Arg 260 265 270 Gln Thr Val Lys ValAla Ser Val Phe Tyr Thr Val Val Asn Pro 275 280 285 Met Leu Asn Pro LeuIle Tyr Ser Leu Arg Asn Lys Asp Val Lys 290 295 300 Asp Ala Phe Trp LysLeu Ile His Thr Gln Val Pro Phe His 305 310 62 210 PRT Homo sapiensmisc_feature Incyte ID No 7476047CD1 62 Met Phe Phe Leu His Gly Phe ThrPhe Met Glu Ser Gly Val Leu 1 5 10 15 Val Ala Thr Ala Phe Asp Arg TyrVal Ala Ile Cys Asp Pro Leu 20 25 30 Arg Tyr Thr Thr Ile Leu Thr Asn SerArg Ile Ile Gln Met Gly 35 40 45 Leu Leu Met Ile Thr Arg Ala Ile Val LeuIle Leu Pro Leu Leu 50 55 60 Leu Leu Leu Lys Pro Leu Tyr Phe Cys Arg MetAsn Ala Leu Ser 65 70 75 His Ser Tyr Cys Tyr His Pro Asp Val Ile Gln LeuAla Cys Ser 80 85 90 Asp Ile Arg Ala Asn Ser Ile Cys Gly Leu Ile Asp LeuIle Leu 95 100 105 Thr Thr Gly Ile Asp Thr Pro Cys Ile Val Leu Ser TyrIle Leu 110 115 120 Ile Ile Arg Phe Val Leu Arg Ile Ala Ser Pro Glu GluTrp His 125 130 135 Lys Val Phe Ser Thr Cys Val Ser His Val Gly Ala ValAla Phe 140 145 150 Phe Tyr Ile His Met Leu Ser Leu Ser Leu Val Tyr ArgTyr Gly 155 160 165 Arg Ser Ala Pro Arg Val Val His Ser Val Met Ala AsnVal Tyr 170 175 180 Leu Leu Leu Pro Pro Val Leu Asn Pro Ile Ile Tyr SerVal Lys 185 190 195 Thr Lys Gln Ile Arg Lys Ala Met Leu Ser Leu Leu LeuThr Lys 200 205 210 63 924 PRT Homo sapiens misc_feature Incyte ID No7289994CD1 63 Met Cys Tyr Gln Cys Arg Leu Cys Ser Asp Val Phe Phe AspPhe 1 5 10 15 Thr Gly Thr Asp Asn Gly Glu Ala Leu Pro Glu Ser Ile ProSer 20 25 30 Ala Pro Gly Thr Leu Pro His Phe Ile Glu Glu Pro Asp Asp Ala35 40 45 Tyr Ile Ile Lys Ser Asn Pro Ile Ala Leu Arg Cys Lys Ala Arg 5055 60 Pro Ala Met Gln Ile Phe Phe Lys Cys Asn Gly Glu Trp Val His 65 7075 Gln Asn Glu His Val Ser Glu Glu Thr Leu Asp Glu Ser Ser Gly 80 85 90Leu Lys Val Arg Glu Val Phe Ile Asn Val Thr Arg Gln Gln Val 95 100 105Glu Asp Phe His Gly Pro Glu Asp Tyr Trp Cys Gln Cys Val Ala 110 115 120Trp Ser His Leu Gly Thr Ser Lys Ser Arg Lys Ala Ser Val Arg 125 130 135Ile Ala Tyr Leu Arg Lys Asn Phe Glu Gln Asp Pro Gln Gly Arg 140 145 150Glu Val Pro Ile Glu Gly Met Ile Val Leu His Cys Arg Pro Pro 155 160 165Glu Gly Val Pro Ala Ala Glu Val Glu Trp Leu Lys Asn Glu Glu 170 175 180Pro Ile Asp Ser Glu Gln Asp Glu Asn Ile Asp Thr Arg Ala Asp 185 190 195His Asn Leu Ile Ile Arg Gln Ala Arg Leu Ser Asp Ser Gly Asn 200 205 210Tyr Thr Cys Met Ala Ala Asn Ile Val Ala Lys Arg Arg Ser Leu 215 220 225Ser Ala Thr Val Val Val Tyr Val Asn Gly Gly Trp Ser Ser Trp 230 235 240Thr Glu Trp Ser Ala Cys Asn Val Arg Cys Gly Arg Gly Trp Gln 245 250 255Lys Arg Ser Arg Thr Cys Thr Asn Pro Ala Pro Leu Asn Gly Gly 260 265 270Ala Phe Cys Glu Gly Met Ser Val Gln Lys Ile Thr Cys Thr Ser 275 280 285Leu Cys Pro Val Asp Gly Ser Trp Glu Val Trp Ser Glu Trp Ser 290 295 300Val Cys Ser Pro Glu Cys Glu His Leu Arg Ile Arg Glu Cys Thr 305 310 315Ala Pro Pro Pro Arg Asn Gly Gly Lys Phe Cys Glu Gly Leu Ser 320 325 330Gln Glu Ser Glu Asn Cys Thr Asp Gly Leu Cys Ile Leu Gly Ile 335 340 345Glu Asn Ala Ser Asp Ile Ala Leu Tyr Ser Gly Leu Gly Ala Ala 350 355 360Val Val Ala Val Ala Val Leu Val Ile Gly Val Thr Leu Tyr Arg 365 370 375Arg Ser Gln Ser Asp Tyr Gly Val Asp Val Ile Asp Ser Ser Ala 380 385 390Leu Thr Gly Gly Phe Gln Thr Phe Asn Phe Lys Thr Val Arg Gln 395 400 405Gly Asn Ser Leu Leu Leu Asn Ser Ala Met Gln Pro Asp Leu Thr 410 415 420Val Ser Arg Thr Tyr Ser Gly Pro Ile Cys Leu Gln Asp Pro Leu 425 430 435Asp Lys Glu Leu Met Thr Glu Ser Ser Leu Phe Asn Pro Leu Ser 440 445 450Asp Ile Lys Val Lys Val Gln Ser Ser Phe Met Val Ser Leu Gly 455 460 465Val Ser Glu Arg Ala Glu Tyr His Gly Lys Asn His Ser Arg Thr 470 475 480Phe Pro His Gly Asn Asn His Ser Phe Ser Thr Met His Pro Arg 485 490 495Asn Lys Met Pro Tyr Ile Gln Asn Leu Ser Ser Leu Pro Thr Arg 500 505 510Thr Glu Leu Arg Thr Thr Gly Val Phe Gly His Leu Gly Gly Arg 515 520 525Leu Val Met Pro Asn Thr Gly Val Ser Leu Leu Ile Pro His Gly 530 535 540Ala Ile Pro Glu Glu Asn Ser Trp Glu Ile Tyr Met Ser Ile Asn 545 550 555Gln Gly Glu Pro Ser Leu Gln Ser Asp Gly Ser Glu Val Leu Leu 560 565 570Ser Pro Glu Val Thr Cys Gly Pro Pro Asp Met Ile Val Thr Thr 575 580 585Pro Phe Ala Leu Thr Ile Pro His Cys Ala Asp Val Ser Ser Glu 590 595 600His Trp Asn Ile His Leu Lys Lys Arg Thr Gln Gln Gly Lys Trp 605 610 615Glu Glu Val Met Ser Val Glu Asp Glu Ser Thr Ser Cys Tyr Cys 620 625 630Leu Leu Asp Pro Phe Ala Cys His Val Leu Leu Asp Ser Phe Gly 635 640 645Thr Tyr Ala Leu Thr Gly Glu Pro Ile Thr Asp Cys Ala Val Lys 650 655 660Gln Leu Lys Val Ala Val Phe Gly Cys Met Ser Cys Asn Ser Leu 665 670 675Asp Tyr Asn Leu Arg Val Tyr Cys Val Asp Asn Thr Pro Cys Ala 680 685 690Phe Gln Glu Val Val Ser Asp Glu Arg His Gln Gly Gly Gln Leu 695 700 705Leu Glu Glu Pro Lys Leu Leu His Phe Lys Gly Asn Thr Phe Ser 710 715 720Leu Gln Ile Ser Val Leu Asp Ile Pro Pro Phe Leu Trp Arg Ile 725 730 735Lys Pro Phe Thr Ala Cys Gln Glu Val Pro Phe Ser Arg Val Trp 740 745 750Cys Ser Asn Arg Gln Pro Leu His Cys Ala Phe Ser Leu Glu Arg 755 760 765Tyr Thr Pro Thr Thr Thr Gln Leu Ser Cys Lys Ile Cys Ile Arg 770 775 780Gln Leu Lys Gly His Glu Gln Ile Leu Gln Val Gln Thr Ser Ile 785 790 795Leu Glu Ser Glu Arg Glu Thr Ile Thr Phe Phe Ala Gln Glu Asp 800 805 810Ser Thr Phe Pro Ala Gln Thr Gly Pro Lys Ala Phe Lys Ile Pro 815 820 825Tyr Ser Ile Arg Gln Arg Ile Cys Ala Thr Phe Asp Thr Pro Asn 830 835 840Ala Lys Gly Lys Asp Trp Gln Met Leu Ala Gln Lys Asn Ser Ile 845 850 855Asn Arg Asn Leu Ser Tyr Phe Ala Thr Gln Ser Ser Pro Ser Ala 860 865 870Val Ile Leu Asn Leu Trp Glu Ala Arg His Gln His Asp Gly Asp 875 880 885Leu Asp Ser Leu Ala Cys Ala Leu Glu Glu Ile Gly Arg Thr His 890 895 900Thr Lys Leu Ser Asn Ile Ser Glu Ser Gln Leu Asp Glu Ala Asp 905 910 915Phe Asn Tyr Ser Arg Gln Asn Gly Leu 920 64 313 PRT Homo sapiensmisc_feature Incyte ID No 7482840CD1 64 Met Ser Ile Ile Asn Thr Ser TyrVal Glu Ile Thr Thr Phe Phe 1 5 10 15 Leu Val Gly Met Pro Gly Leu GluTyr Ala His Ile Trp Ile Ser 20 25 30 Ile Pro Ile Cys Ser Met Tyr Leu IleAla Ile Leu Gly Asn Gly 35 40 45 Thr Ile Leu Phe Ile Ile Lys Thr Glu ProSer Leu His Glu Pro 50 55 60 Met Tyr Tyr Phe Leu Ser Met Leu Ala Met SerAsp Leu Gly Leu 65 70 75 Ser Leu Ser Ser Leu Pro Thr Val Leu Ser Ile PheLeu Phe Asn 80 85 90 Ala Pro Glu Ile Ser Ser Asn Ala Cys Phe Ala Gln GluPhe Phe 95 100 105 Ile His Gly Phe Ser Val Leu Glu Ser Ser Val Leu LeuIle Met 110 115 120 Ser Phe Asp Arg Phe Leu Ala Ile His Asn Pro Leu ArgTyr Thr 125 130 135 Ser Ile Leu Thr Thr Val Arg Val Ala Gln Ile Gly IleVal Phe 140 145 150 Ser Phe Lys Ser Met Leu Leu Val Leu Pro Phe Pro PheThr Leu 155 160 165 Arg Asn Leu Arg Tyr Cys Lys Lys Asn Gln Leu Ser HisSer Tyr 170 175 180 Cys Leu His Gln Asp Val Met Lys Leu Ala Cys Ser AspAsn Arg 185 190 195 Ile Asp Val Ile Tyr Gly Phe Phe Gly Ala Leu Cys LeuMet Val 200 205 210 Asp Phe Ile Leu Ile Ala Val Ser Tyr Thr Leu Ile LeuLys Thr 215 220 225 Val Leu Gly Ile Ala Ser Lys Lys Glu Gln Leu Lys AlaLeu Asn 230 235 240 Thr Cys Val Ser His Ile Cys Ala Val Ile Ile Phe TyrLeu Pro 245 250 255 Ile Ile Asn Leu Ala Val Val His Arg Phe Ala Arg HisVal Ser 260 265 270 Pro Leu Ile Asn Val Leu Met Ala Asn Val Leu Leu LeuVal Pro 275 280 285 Pro Leu Thr Asn Pro Ile Val Tyr Cys Val Lys Thr LysGln Ile 290 295 300 Arg Val Arg Val Val Ala Lys Leu Cys Gln Arg Lys Ile305 310 65 320 PRT Homo sapiens misc_feature Incyte ID No 55093631CD1 65Met Pro Ser Gly Ser Ala Met Ile Ile Phe Asn Leu Ser Ser Tyr 1 5 10 15Asn Pro Gly Pro Phe Ile Leu Val Gly Ile Pro Gly Leu Glu Gln 20 25 30 PheHis Val Trp Ile Gly Ile Pro Phe Cys Ile Ile Tyr Ile Val 35 40 45 Ala ValVal Gly Asn Cys Ile Leu Leu Tyr Leu Ile Val Val Glu 50 55 60 His Ser LeuHis Glu Pro Met Phe Phe Phe Leu Ser Met Leu Ala 65 70 75 Met Thr Asp LeuIle Leu Ser Thr Ala Gly Val Pro Lys Ala Leu 80 85 90 Ser Ile Phe Trp LeuGly Ala Arg Val Ile Thr Phe Pro Gly Cys 95 100 105 Leu Thr Gln Met PhePhe Leu His Tyr Asn Phe Val Leu Asp Ser 110 115 120 Ala Ile Leu Met AlaMet Ala Ser Asp His Tyr Val Ala Ile Cys 125 130 135 Ser Pro Leu Arg TyrThr Thr Ile Leu Thr Pro Lys Thr Ile Ile 140 145 150 Lys Ser Ala Met GlyIle Ser Phe Arg Ser Phe Cys Ile Ile Leu 155 160 165 Pro Asp Val Phe LeuLeu Thr Cys Leu Pro Phe Cys Arg Thr Arg 170 175 180 Ile Ile Pro His ThrTyr Cys Glu His Ile Gly Val Ala Gln Leu 185 190 195 Ala Cys Ala Asp IleSer Ile Asn Phe Trp Tyr Gly Phe Cys Val 200 205 210 Pro Ile Met Thr ValIle Ser Asp Val Ile Leu Ile Ala Val Ser 215 220 225 Tyr Ala His Ile LeuCys Ala Val Phe Gly Leu Pro Ser Gln Asp 230 235 240 Ala Cys Gln Lys AlaLeu Gly Thr Cys Gly Ser His Val Cys Val 245 250 255 Ile Leu Met Phe TyrThr Pro Ala Phe Phe Ser Ile Leu Ala His 260 265 270 Arg Phe Gly His AsnVal Ser Arg Thr Phe His Ile Met Phe Ala 275 280 285 Asn Leu Tyr Ile ValIle Pro Pro Ala Leu Asn Pro Met Val Tyr 290 295 300 Gly Val Lys Thr LysGln Ile Arg Asp Lys Val Ile Leu Leu Phe 305 310 315 Ser Lys Gly Thr Gly320 66 313 PRT Homo sapiens misc_feature Incyte ID No 7474992CD1 66 MetGly Asp Arg Gly Thr Ser Asn His Ser Glu Met Thr Asp Phe 1 5 10 15 IleLeu Ala Gly Phe Arg Val Arg Pro Glu Leu His Ile Leu Leu 20 25 30 Phe LeuLeu Phe Leu Phe Val Tyr Ala Met Ile Leu Leu Gly Asn 35 40 45 Val Gly MetMet Thr Ile Ile Met Thr Asp Pro Arg Leu Asn Thr 50 55 60 Pro Met Tyr PhePhe Leu Gly Asn Leu Ser Phe Ile Asp Leu Phe 65 70 75 Tyr Ser Ser Val IleGlu Pro Lys Ala Met Ile Asn Phe Trp Ser 80 85 90 Glu Asn Lys Ser Ile SerPhe Ala Gly Cys Val Ala Gln Leu Phe 95 100 105 Leu Phe Ala Leu Leu IleVal Thr Glu Gly Phe Leu Leu Ala Ala 110 115 120 Met Ala Tyr Asp Arg PheIle Ala Ile Cys Asn Pro Leu Leu Tyr 125 130 135 Ser Val Gln Met Ser ThrArg Leu Cys Thr Gln Leu Val Ala Gly 140 145 150 Ser Tyr Phe Cys Gly CysIle Ser Ser Val Ile Gln Thr Ser Met 155 160 165 Thr Phe Thr Leu Ser PheCys Ala Ser Arg Ala Val Asp His Phe 170 175 180 Tyr Cys Asp Ser Arg ProLeu Gln Arg Leu Ser Cys Ser Asp Leu 185 190 195 Phe Ile His Arg Met IleSer Phe Ser Leu Ser Cys Ile Ile Ile 200 205 210 Leu Pro Thr Ile Ile ValIle Ile Val Ser Tyr Met Tyr Ile Val 215 220 225 Ser Thr Val Leu Lys IleHis Ser Thr Glu Gly His Lys Lys Ala 230 235 240 Phe Ser Thr Cys Ser SerHis Leu Gly Val Val Ser Val Leu Tyr 245 250 255 Gly Ala Val Phe Phe MetTyr Leu Thr Pro Asp Arg Phe Pro Glu 260 265 270 Leu Ser Lys Val Ala SerLeu Cys Tyr Ser Leu Val Thr Pro Met 275 280 285 Leu Asn Pro Leu Ile TyrSer Leu Arg Asn Lys Asp Val Gln Glu 290 295 300 Ala Leu Lys Lys Phe LeuGlu Lys Lys Asn Ile Ile Leu 305 310 67 310 PRT Homo sapiens misc_featureIncyte ID No 7476244CD1 67 Met Gln Gln Asn Asn Ser Val Pro Glu Phe IleLeu Leu Gly Leu 1 5 10 15 Thr Gln Asp Pro Leu Arg Gln Lys Ile Val PheVal Ile Phe Leu 20 25 30 Ile Phe Tyr Met Gly Thr Val Val Gly Asn Met LeuIle Ile Val 35 40 45 Thr Ile Lys Ser Ser Arg Thr Leu Gly Ser Pro Met TyrPhe Phe 50 55 60 Leu Phe Tyr Leu Ser Phe Ala Asp Ser Cys Phe Ser Thr SerThr 65 70 75 Ala Pro Arg Leu Ile Val Asp Ala Leu Ser Glu Lys Lys Ile Ile80 85 90 Thr Tyr Asn Glu Cys Met Thr Gln Val Phe Ala Leu His Leu Phe 95100 105 Gly Cys Met Glu Ile Phe Val Leu Ile Leu Met Ala Val Asp Arg 110115 120 Tyr Val Ala Ile Cys Lys Pro Leu Arg Tyr Pro Thr Ile Met Ser 125130 135 Gln Gln Val Cys Ile Ile Leu Ile Val Leu Ala Trp Ile Gly Ser 140145 150 Leu Ile His Ser Thr Ala Gln Ile Ile Leu Ala Leu Arg Leu Pro 155160 165 Phe Cys Gly Pro Tyr Leu Ile Asp His Tyr Cys Cys Asp Leu Gln 170175 180 Pro Leu Leu Lys Leu Ala Cys Met Asp Thr Tyr Met Ile Asn Leu 185190 195 Leu Leu Val Ser Asn Ser Gly Ala Ile Cys Ser Ser Ser Phe Met 200205 210 Ile Leu Ile Ile Ser Tyr Ile Val Ile Leu His Ser Leu Arg Asn 215220 225 His Ser Ala Lys Gly Lys Lys Lys Ala Leu Ser Ala Cys Thr Ser 230235 240 His Ile Ile Val Val Ile Leu Phe Phe Gly Pro Cys Ile Phe Ile 245250 255 Tyr Thr Arg Pro Pro Thr Thr Phe Pro Met Asp Lys Met Val Ala 260265 270 Val Phe Tyr Thr Ile Gly Thr Pro Phe Leu Asn Pro Leu Ile Tyr 275280 285 Thr Leu Arg Asn Ala Glu Val Lys Asn Ala Met Arg Lys Leu Trp 290295 300 His Gly Lys Ile Ile Ser Glu Asn Lys Gly 305 310 68 318 PRT Homosapiens misc_feature Incyte ID No 7487604CD1 68 Met Asp Lys Ile Asn GlnThr Phe Val Arg Glu Phe Ile Leu Leu 1 5 10 15 Gly Leu Ser Gly Tyr ProLys Leu Glu Ile Ile Phe Phe Ala Leu 20 25 30 Ile Leu Val Met Tyr Val ValIle Leu Ile Gly Asn Gly Val Leu 35 40 45 Ile Ile Ala Ser Ile Leu Asp SerArg Leu His Met Pro Met Tyr 50 55 60 Phe Phe Leu Gly Asn Leu Ser Phe LeuAsp Ile Cys Tyr Thr Thr 65 70 75 Ser Ser Ile Pro Ser Thr Leu Val Ser LeuIle Ser Lys Lys Arg 80 85 90 Asn Ile Ser Phe Ser Gly Cys Ala Val Gln MetPhe Phe Gly Phe 95 100 105 Ala Met Gly Ser Thr Glu Cys Phe Leu Leu GlyMet Met Ala Phe 110 115 120 Asp Arg Tyr Val Ala Ile Cys Asn Pro Leu ArgTyr Pro Ile Ile 125 130 135 Met Asn Lys Val Val Tyr Val Leu Leu Thr SerVal Ser Trp Leu 140 145 150 Ser Gly Gly Ile Asn Ser Thr Val Gln Thr SerLeu Ala Met Arg 155 160 165 Trp Pro Phe Cys Gly Asn Asn Ile Ile Asn HisPhe Leu Cys Glu 170 175 180 Ile Leu Ala Val Leu Lys Leu Ala Cys Ser AspIle Ser Val Asn 185 190 195 Ile Val Thr Leu Ala Val Ser Asn Ile Ala PheLeu Val Leu Pro 200 205 210 Leu Leu Val Ile Phe Phe Ser Tyr Met Phe IleLeu Tyr Thr Ile 215 220 225 Leu Arg Thr Asn Ser Ala Thr Gly Arg His LysAla Phe Ser Thr 230 235 240 Cys Ser Ala His Leu Thr Val Val Ile Ile PheTyr Gly Thr Ile 245 250 255 Phe Phe Met Tyr Ala Lys Pro Lys Ser Gln AspLeu Leu Gly Lys 260 265 270 Asp Asn Leu Gln Ala Thr Glu Gly Leu Val SerMet Phe Tyr Gly 275 280 285 Val Val Thr Pro Met Leu Asn Pro Ile Ile TyrSer Leu Arg Asn 290 295 300 Lys Asp Val Lys Ala Ala Ile Lys Tyr Leu LeuSer Arg Lys Ala 305 310 315 Ile Asn Gln 69 313 PRT Homo sapiensmisc_feature Incyte ID No 7483200CD1 69 Met Glu Lys Asn Asn Leu Thr AlaVal Thr Gln Phe Ile Leu Met 1 5 10 15 Gly Ile Thr Glu Arg Pro Glu LeuGln Ala Pro Leu Phe Gly Leu 20 25 30 Phe Leu Val Ile Tyr Leu Ser Ser MetPhe Gly Asn Leu Gly Met 35 40 45 Ile Ile Leu Thr Thr Val Asp Ser Lys LeuGln Thr Pro Met Tyr 50 55 60 Phe Phe Ile Arg His Leu Ala Ile Thr Asp LeuGly Tyr Ser Thr 65 70 75 Ala Val Gly Pro Lys Met Leu Val Asn Phe Val ValAsp Leu Asn 80 85 90 Ile Ile Ser Tyr Asn Leu Cys Ala Thr Gln Leu Ala PhePhe Leu 95 100 105 Val Phe Ile Ile Ser Glu Leu Leu Ile Leu Ser Ala MetSer Tyr 110 115 120 Asp Arg Tyr Val Ala Ile Cys Lys Pro Leu Leu Tyr ThrVal Ile 125 130 135 Met Ser Gln Arg Val Cys Gln Val Leu Val Ala Ile ProTyr Leu 140 145 150 Tyr Cys Thr Phe Val Ser Leu Leu Val Thr Ile Lys IlePhe Thr 155 160 165 Leu Ser Phe Cys Gly Tyr Asn Val Ile Ser His Phe TyrCys Asp 170 175 180 Ser Leu Pro Leu Leu Ser Leu Ile Cys Ser Asn Thr AsnGlu Ile 185 190 195 Glu Met Ile Ile Leu Val Leu Ala Ala Phe Asn Leu IleSer Ser 200 205 210 Leu Leu Val Val Leu Val Ser Tyr Leu Phe Ile Leu IleAla Ile 215 220 225 Leu Arg Met Asn Ser Ala Glu Gly Arg Arg Lys Ala PheSer Thr 230 235 240 Cys Gly Ser His Leu Thr Val Val Thr Val Phe Tyr GlyThr Leu 245 250 255 Ile Phe Met Tyr Val Gln Pro Gln Ser Ser His Ser PheAsp Thr 260 265 270 Asp Lys Val Ala Ser Ile Phe Tyr Thr Leu Ile Ile ProMet Leu 275 280 285 Asn Pro Met Ile Tyr Ser Leu Arg Asn Lys Asp Val LysTyr Ala 290 295 300 Leu Gln Arg Ser Leu Lys Lys Ile Tyr Ser Ile Leu Ser305 310 70 224 PRT Homo sapiens misc_feature Incyte ID No 7476069CD1 70Met Phe Ser Cys Asn Thr Ser Thr Ser Gly Gln Ser Thr Phe Leu 1 5 10 15Leu Thr Gly Phe Pro Gly Leu Glu Ala Ser His His Trp Val Ser 20 25 30 IlePro Ile Asn Leu Phe Cys Val Val Ser Ile Leu Gly Asn Asn 35 40 45 Ile IleLeu Phe Leu Ile His Thr Asp Pro Ala Leu His Glu Pro 50 55 60 Met Tyr IlePhe Leu Ser Met Leu Ala Ala Ser Asp Leu Gly Leu 65 70 75 Cys Ala Ser ThrPhe Pro Thr Met Val Arg Leu Phe Trp Leu Gly 80 85 90 Ala Arg Glu Leu ProPhe Asp Leu Cys Ala Ala Gln Met Phe Phe 95 100 105 Ile His Thr Phe ThrTyr Val Glu Ser Gly Val Leu Leu Ala Met 110 115 120 Ala Phe Asp Arg PheIle Ala Ile Arg Asp Pro Leu His Tyr Ala 125 130 135 Ile Ile Ile Thr CysSer Val Thr Ala Glu Val Gly Thr Ala Ile 140 145 150 Leu Val Arg Ala ValLeu Leu Asn Leu Pro Gly Pro Ile Leu Leu 155 160 165 Gln Gln Leu Leu PhePro Lys Ile Ser Ala Leu Cys His Cys Tyr 170 175 180 Cys Leu His Cys AspLeu Val Gly Leu Ala Cys Ser Asp Thr Gln 185 190 195 Ile Asn Ser Leu ValGly Leu Val Ser Ile Leu Phe Ser Leu Cys 200 205 210 Leu Asp Ser Phe LeuIle Met Leu Ser Tyr Ala Leu Ile Leu 215 220 71 314 PRT Homo sapiensmisc_feature Incyte ID No 7472453CD1 71 Met Gly Val Lys Asn His Ser ThrVal Thr Glu Phe Leu Leu Ser 1 5 10 15 Gly Leu Thr Glu Gln Ala Glu LeuGln Leu Pro Leu Phe Cys Leu 20 25 30 Phe Leu Gly Ile Tyr Thr Val Thr ValVal Gly Asn Leu Ser Met 35 40 45 Ile Ser Ile Ile Arg Leu Asn Arg Gln LeuHis Thr Pro Met Tyr 50 55 60 Tyr Phe Leu Ser Ser Leu Ser Phe Leu Asp PheCys Tyr Ser Ser 65 70 75 Val Ile Thr Pro Lys Met Leu Ser Gly Phe Leu CysArg Asp Arg 80 85 90 Ser Ile Ser Tyr Ser Gly Cys Met Ile Gln Leu Phe PhePhe Cys 95 100 105 Val Cys Val Ile Ser Glu Cys Tyr Met Leu Ala Ala MetAla Cys 110 115 120 Asp Arg Tyr Val Ala Ile Cys Ser Pro Leu Leu Tyr ArgVal Ile 125 130 135 Met Ser Pro Arg Val Cys Ser Leu Leu Val Ala Ala ValPhe Ser 140 145 150 Val Gly Phe Thr Asp Ala Val Ile His Gly Gly Cys IleLeu Arg 155 160 165 Leu Ser Phe Cys Gly Ser Asn Ile Ile Lys His Tyr PheCys Asp 170 175 180 Ile Val Pro Leu Ile Lys Leu Ser Cys Ser Ser Thr TyrIle Asp 185 190 195 Glu Leu Leu Ile Phe Val Ile Gly Gly Phe Asn Met ValAla Thr 200 205 210 Ser Leu Thr Ile Ile Ile Ser Tyr Ala Phe Ile Leu ThrSer Ile 215 220 225 Leu Arg Ile His Ser Lys Lys Gly Arg Cys Lys Ala PheSer Thr 230 235 240 Cys Ser Ser His Leu Thr Ala Val Leu Met Phe Tyr GlySer Leu 245 250 255 Met Ser Met Tyr Leu Lys Pro Ala Ser Ser Ser Ser LeuThr Gln 260 265 270 Glu Lys Val Ser Ser Val Phe Tyr Thr Thr Val Ile LeuMet Leu 275 280 285 Asn Pro Leu Ile Tyr Ser Leu Arg Asn Asn Glu Val ArgAsn Ala 290 295 300 Leu Met Lys Leu Leu Arg Arg Lys Ile Ser Leu Ser ProGly 305 310 72 320 PRT Homo sapiens misc_feature Incyte ID No 5492483CD172 Met Lys Thr Gly Asn Gln Ser Phe Gly Thr Asp Phe Leu Leu Val 1 5 10 15Gly Leu Phe Gln Tyr Gly Trp Ile Asn Ser Leu Leu Phe Val Val 20 25 30 IleAla Thr Leu Phe Thr Val Ala Leu Thr Gly Asn Ile Met Leu 35 40 45 Ile HisLeu Ile Arg Leu Asn Thr Arg Leu His Thr Pro Met Tyr 50 55 60 Phe Leu LeuSer Gln Leu Ser Ile Val Asp Leu Met Tyr Ile Ser 65 70 75 Thr Thr Val ProLys Met Ala Val Ser Phe Leu Ser Gln Ser Lys 80 85 90 Thr Ile Arg Phe LeuGly Cys Glu Ile Gln Thr Tyr Val Phe Leu 95 100 105 Ala Leu Gly Gly ThrGlu Ala Leu Leu Leu Gly Phe Met Ser Tyr 110 115 120 Asp Arg Tyr Val AlaIle Cys His Pro Leu His Tyr Pro Met Leu 125 130 135 Met Ser Lys Lys IleCys Cys Leu Met Val Ala Cys Ala Trp Ala 140 145 150 Ser Gly Ser Ile AsnAla Phe Ile His Thr Leu Tyr Val Phe Gln 155 160 165 Leu Pro Phe Cys ArgSer Arg Leu Ile Asn His Phe Phe Cys Glu 170 175 180 Val Pro Ala Leu LeuSer Leu Val Cys Gln Asp Thr Ser Gln Tyr 185 190 195 Glu Tyr Thr Val LeuLeu Ser Gly Leu Ile Ile Leu Leu Leu Pro 200 205 210 Phe Leu Ala Ile LeuAla Ser Tyr Ala Arg Val Leu Ile Val Val 215 220 225 Phe Gln Met Ser SerGly Lys Gly Gln Ala Lys Ala Val Ser Thr 230 235 240 Cys Ser Ser His LeuIle Val Ala Ser Leu Phe Tyr Ala Thr Thr 245 250 255 Leu Phe Thr Tyr ThrArg Pro His Ser Leu Arg Ser Pro Ser Arg 260 265 270 Asp Lys Ala Val AlaVal Phe Tyr Thr Ile Val Thr Pro Leu Leu 275 280 285 Asn Pro Phe Ile TyrSer Leu Arg Asn Lys Glu Val Thr Gly Ala 290 295 300 Val Arg Arg Leu LeuGly Tyr Trp Ile Cys Cys Arg Lys Tyr Asp 305 310 315 Phe Arg Ser Leu Tyr320 73 318 PRT Homo sapiens misc_feature Incyte ID No 7472079CD1 73 MetIle Gln Pro Met Ala Ser Pro Ser Asn Ser Ser Thr Val Pro 1 5 10 15 ValSer Glu Phe Leu Leu Thr Cys Phe Pro Asn Phe Gln Ser Trp 20 25 30 Gln HisTrp Leu Ser Leu Pro Leu Ser Leu Leu Phe Leu Leu Ala 35 40 45 Met Gly AlaAsn Thr Thr Leu Leu Ile Thr Ile Gln Leu Glu Ala 50 55 60 Ser Leu His GlnPro Leu Tyr Tyr Leu Leu Ser Leu Leu Ser Leu 65 70 75 Leu Asp Ile Val LeuCys Leu Thr Val Ile Pro Lys Val Leu Ala 80 85 90 Ile Phe Trp Tyr Asp LeuArg Ser Ile Ser Phe Pro Ala Cys Phe 95 100 105 Leu Gln Met Phe Ile MetAsn Ser Phe Leu Pro Met Glu Ser Cys 110 115 120 Thr Phe Met Val Met AlaTyr Asp Arg Tyr Val Ala Ile Cys His 125 130 135 Pro Leu Arg Tyr Pro SerIle Ile Thr Asn Gln Phe Val Ala Lys 140 145 150 Ala Ser Val Phe Ile ValVal Arg Asn Ala Leu Leu Thr Ala Pro 155 160 165 Ile Pro Ile Leu Thr SerLeu Leu His Tyr Cys Gly Glu Asn Val 170 175 180 Ile Glu Asn Cys Ile CysAla Asn Leu Ser Val Ser Arg Leu Ser 185 190 195 Cys Asp Asn Phe Thr LeuAsn Arg Ile Tyr Gln Phe Val Ala Gly 200 205 210 Trp Thr Leu Leu Gly SerAsp Leu Phe Leu Ile Phe Leu Ser Tyr 215 220 225 Thr Phe Ile Leu Arg AlaVal Leu Arg Phe Lys Ala Glu Gly Ala 230 235 240 Ala Val Lys Ala Leu SerThr Cys Gly Ser His Phe Ile Leu Ile 245 250 255 Leu Phe Phe Ser Thr IleLeu Leu Val Val Val Leu Thr Asn Val 260 265 270 Ala Arg Lys Lys Val ProMet Asp Ile Leu Ile Leu Leu Asn Val 275 280 285 Leu His His Leu Ile ProPro Ala Leu Asn Pro Ile Val Tyr Gly 290 295 300 Val Arg Thr Lys Glu IleLys Gln Gly Ile Gln Lys Leu Leu Gln 305 310 315 Arg Gly Arg 74 930 DNAHomo sapiens misc_feature Incyte ID No 7475222CB1 74 atggccagtacaagtaatgt gactgagttg attttcaccg gccttttcca ggatccagct 60 gtgcagagtgtatgctttgt ggtgtttctc cccgtgtacc ttgccacggt ggtgggcaat 120 ggcctcatcgttctgacggt cagtatcagc aagagtctgg attctcccat gtacttcttc 180 cttagcggcctgtccttggt ggagatcagt tattcctcca ctatcgcccc taaattcatc 240 atagacttactcgccaagat taaaaccatc tctctggaag gctgtctgac tcagatattc 300 ttcttccacttctttggggt tgctgagatc cttttgattg tggtgatggc ctatgattgc 360 tacgtggccatttgcaagcc tcttcattat atttacatta tcagtcgtca actgtgtcac 420 cttctggtggatggtttccg gctggggggc ttttgtcact ccataattca gattctcgtt 480 atcatccaattgcccttctg tggtcccaat gtgattgacc actatttctg tgacctccag 540 cctttattcaagcttgcctg cactgacacc ttcatggagg gggttattgt gttggccaac 600 agtggattattctctgtctt ctccttcctc atcttggtgt cctcttatat tgtcattctg 660 gtcaacttgaggaaccattc tgcagagggg aggcacaaag ccctctccac ctgtgcttct 720 cacatcacagtggtcatctt gttttttgga cctgctatct tcctctacat gcgaccttct 780 tccactttcactgaagataa acttgtggct gtattctaca cggtcatcac ccccatgctg 840 aaccccatcatttacacact caggaatgca gaggtgaaaa tcgccataag aagattgtgg 900 agcaaaaaggagaatccagg gagggagtga 930 75 1151 DNA Homo sapiens misc_feature IncyteID No 7476060CB1 75 tctattatac tatgccacag ttatcatttc ttattccaagacataccatt tttttccttc 60 aaatttccct agtgccctcc agctgatata aacatgagccctgagaacca gagcagcgtg 120 tccgagttcc tcctcctggg cctccccatc cggccagagcagcaggccgt gttcttcgcc 180 ctgttcctgg gcatgtacct gaccacggtg ctggggaacctgctcatcat gctgctcatc 240 cagctagact ctcaccttca cacccccatg tacttcttccttagccactt ggccctcact 300 gacatctcct tttcatctgt cactgtccct aagatgctgatgaacatgca gactcagcac 360 ctagccgtct tttacaaggg atgcatttca cagacatattttttcatatt ttttgctgac 420 ttagacagtt tccttatcac ttcaatggca tatgacaggtatgtggccat ctgtcatcct 480 ctacattatg ccaccatcat gactcagagc cagtgtgtcatgctggtggc tgggtcctgg 540 gtcatcgctt gtgcgtgtgc tcttttgcat accctcctcctggcccagct ttccttctgt 600 gctgaccaca tcatccctca ctacttctgt gaccttggtgccctgctcaa gttgtcctgc 660 tcagacacct ccctcaatca gttagcaatc tttacagcagcattgacagc cattatgctt 720 ccattcctgt gcatcctggt ttcttatggt cacattggggtcaccatcct ccagattccc 780 tctaccaagg gcatatgcaa agccttgtcc acttgtggatcccacctctc agtggtgact 840 atctattatc ggacaattat tggtctctat tttcttcccccatccagcaa caccaatgac 900 aagaacataa ttgcttcagt gatatacaca gcagtcactcccatgttgaa cccattcatt 960 tacagtctga gaaataaaga cattaaggga gccctaagaaaactcttgag taggtcaggc 1020 gcagtggctc atgcctgtaa tctcagcact ttgggaggctgaggcagacg gatcacctga 1080 gatcaggagt tcgagaccag cctggccaac atggcgaaacccagtctcta ctaaaaatac 1140 aaaaaaatta g 1151 76 1551 DNA Homo sapiensmisc_feature Incyte ID No 7476084CB1 76 agcgattctc atgcctcagt tttgcaggtagctgagatta cagttgcctg cacctggctt 60 atttttgtat ttttagtaga gacagggtttcaccatgttg gccaggctgg tcttgaactc 120 ctgacctcaa gtgttccccc tgcctcggcctcccaaagtg ctgggattac aggcatgaac 180 caccatcccc agccttctct cttcttaataatggctttct atgtctttca cttctctcat 240 accctcactc tgtttctcct tgactctcccattcctgttt tgttatcttt ctttattgcc 300 gtttctttct gcttttctgt ttatcactcgctggctactt gcctttctct ctctattctc 360 tgtctctgtc cctgtttctt ctgtttcaagttcaatggtt ctctgtctct atctctctgt 420 ttctgcctct ccgtctgtct tttgtttctcttgcatgcag ggccccatac tgtggatcat 480 ggcaaatctg agccagccct ccgaatttgtcctcttgggc ttctcctcct ttggtgagct 540 gcaggccctt ctgtatggcc ccttcctcatgctttatctt ctcgccttca tgggaaacac 600 catcatcata gttatggtca tagctgacacccacctacat acacccatgt acttcttcct 660 gggcaatttt tccctgctgg agatcttggtaaccatgact gcagtgccca ggatgctctc 720 agacctgttg gtcccccaca aagtcattaccttcactggc tgcatggtcc agttctactt 780 ccacttttcc ctggggtcca cctccttcctcatcctgaca gacatggccc ttgatcgctt 840 tgtggccatc tgccacccac tgcgctatggcactctgatg agccgggcta tgtgtgtcca 900 gctggctggg gctgcctggg cagctcctttcctagccatg gtacccactg tcctctcccg 960 agctcatctt gattactgcc atggcgacgtcatcaaccac ttcttctgtg acaatgaacc 1020 tctcctgcag ttgtcatgct ctgacactcgcctgttggaa ttctgggact ttctgatggc 1080 cttgaccttt gtcctcagct ccttcctggtgaccctcatc tcctatggct acatagtgac 1140 cactgtgctg cggatcccct ctgccagcagctgccagaag gctttctcca cttgcgggtc 1200 tcacctcaca ctggtcttca tcggctacagtagtaccatc tttctgtatg tcaggcctgg 1260 caaagctcac tctgtgcaag tcaggaaggtcgtggccttg gtgacttcag ttctcacccc 1320 ctttctcaat ccctttatcc ttaccttctgcaatcagaca gttaaaacag tgctacaggg 1380 gcagatgcag aggctgaaag gcctttgcaaggcacaatga tgagcccagg gcccagggga 1440 acctggcctg cctccattga gcagttctgtggggagggag acctccagca agtgggaaga 1500 acactgctga gtttctttag tttttttccctctgagcaat aactacagtg a 1551 77 1151 DNA Homo sapiens misc_featureIncyte ID No 7476110CB1 77 aactgggatg tgatcgcatc taactttcca aaaccatctccctgtcattc ctataacctc 60 ccctttccat acttccagag gaatcacacc catggaaccaagaaaccaaa ccagtgcatc 120 tcaattcatc ctcctgggac tctcagaaaa gccagagcaggagacgcttc tcttttccct 180 gttcttctgc atgtacctgg tcatggtcgt ggggaacctgctcatcatcc tggccatcag 240 catagactcc cacctccaca cccccatgta cttcttcctggccaacctgt ccctggttga 300 tttctgtctg gccaccaaca ccatccctaa gatgctggtgagccttcaaa ccgggagcaa 360 ggccatctct tatccctgct gcctgatcca gatgtacttcttccatttct ttggcatcgt 420 ggacagcgtc ataatcgcca tgatggctta tgaccggttcgtggccatct gccacccatt 480 gcactacgcc aagatcatga gcctacgcct ctgtcgcctgctggtcggcg ccctctgggc 540 gttttcctgc ttcatctcac tcactcacat cctcctgatggcccgtctcg ttttctgcgg 600 cagccatgag gtgcctcact acttctgcga cctcactcccatcctccgac tttcgtgcac 660 ggacacctct gtgaatagga tcttcatcct cattgtggcagggatggtga tagccacgcc 720 ctttgtctgc atcctggcct cctatgctcg catccttgtggccatcatga aggtcccctc 780 tgcaggcggc aggaagaaag ccttctccac ctgcagctcccacctgtctg tggttgctct 840 cttctatggg accaccattg gcgtctatct gtgtccctcctcggtcctca ccactgtgaa 900 ggagaaagct tctgcggtga tgtacacagc agtcacccccatgctgaatc ccttcatcta 960 cagcttgagg aacagagacc tgaaaggggc tctcaggaagctggtcaaca gaaagatcac 1020 ctcatcttcc tgaccaccag gactcaggaa cttctggggggtagaatata tacatctggg 1080 agtcttgggc taacatctgg aattgcatga gttgaagagtaggcactttg aattttatta 1140 ttattattat t 1151 78 1251 DNA Homo sapiensmisc_feature Incyte ID No 7476774CB1 78 cctcgcagct caaagagtca ttaggaagaccaaatgagat aatgtatgta aaaatactta 60 gtacatcatc cagcatgagt tagcaaaatctccaaatgtt ctttattatt cattctttgg 120 ttacttctgt ttttctaaca gctttgggaccccagaacag aacaatgcat tttgtgactg 180 agtttgtcct cctgggtttc catggtcaaagggagatgca gagctgcttc ttctcattca 240 tcctggttct ctatctcctg acactgctagggaatggagc tattgtctgt gcagtgaaat 300 tggacaggcg gctccacaca cccatgtacatccttctggg aaactttgcc tttctagaga 360 tctggtacat ttcctccact gtcccaaacatgctagtcaa tatcctctct gagattaaaa 420 ccatctcctt ctctggttgc ttcctgcaattctatttctt tttttcactg ggtacaacag 480 agtgtttctt tttatcagtt atggcttatgatcggtacct ggccatctgt cgtccattac 540 actacccctc catcatgact gggaagttctgtataattct ggtctgtgta tgctgggtag 600 gcggatttct ctgctatcca gtccctattgttcttatctc ccaacttccc ttctgtgggc 660 ccaacatcat tgaccacttg gtgtgtgacccaggcccatt gtttgcactg gcctgcatct 720 ctgctccttc cactgagctt atctgttacaccttcaactc gatgattatc tttgggccct 780 tcctctccat cttgggatct tacactctggtcatcagagc tgtgctttgt attccctctg 840 gtgctggtcg aactaaagct ttctccacatgtgggtccca cctaatggtg gtgtctctat 900 tctatggaac ccttatggtg atgtatgtgagcccaacatc agggaaccca gcaggaatgc 960 agaagatcat cactctggta tacacagcaatgactccatt cttaaatccc cttatctata 1020 gtcttcgaaa caaagacatg aaagatgctctaaagagagt cctggggtta acagttagcc 1080 aaaactgaga tatctttgaa aaagaagccaaattggccac ttctgacctt aattttttat 1140 aactatagag agtagcttca gtagtatgttctggctcaca ctcaggtaga cagacttatc 1200 tttcacagtt ccttagcagt taaattcagctcattaatga taaatgccaa t 1251 79 1129 DNA Homo sapiens misc_featureIncyte ID No 7477364CB1 79 gagtctaagt caaatttgat tatagggcct ttagatttgaatccttctct aactttcctt 60 attgttattc agcaggtaag tcaaaggcct gagttgatgtaaatggctgg caacaatttc 120 actgaggtta ccgtcttcat cctctctgga tttgcaaatcaccctgaatt acaagtcagt 180 cttttcttga tgtttctctt catttatcta ttcactgttttgggaaacct gggactgatc 240 acgttaatca gaatggattc tcagcttcac acccctatgtactttttcct gagcaattta 300 gcatttattg acatatttta ctcctctact gtaacacctaaggcattggt gaatttccaa 360 tccaatcgga gatccatctc ctttgttggc tgctttgttcaaatgtactt ttttgttgga 420 ttggtgtgtt gtgagtgttt ccttctggga tcaatggcctacaatcgcta catagcaatc 480 tgcaatccct tactgtattc agtagtcatg tcccaaaaagtgtccaactg gctgggagta 540 atgccatatg tgataggctt cacaagctcg ctgatatctgtctgggtgat aagcagtttg 600 gcgttctgtg attccagcat caatcatttt ttttgtgacaccacagctct tttagcactc 660 tcctgtgtag atacattcgg cacagaaatg gtgagctttgtcttagctgg attcactctt 720 cttagctctc tccttatcat cacagtcact tatatcatcatcatctcagc catcctgagg 780 atccagtcag cagcaggcag gcagaaggcc ttctccacctgcgcatccca cctcatggct 840 gtaactatct tttatgggtc tctgattttc acctatttgcaacctgataa cacatcatcg 900 ctgacccagg cgcaggtggc atctgtattc tatacgattgtcattcccat gctgaatcca 960 ctcatctaca gtctgaggaa caaagatgtg aaaaatgctcttctgagagt catacataga 1020 aaactttttc catgacaaat ttatgtatgt tacaattaaaacaaaggtgg atggcttcag 1080 gaattcagtt atgccaacaa ctaggaaaat agtagagtaacctcaaaaa 1129 80 1301 DNA Homo sapiens misc_feature Incyte ID No7477694CB1 80 ctgagacagg ttaggattcc tactctagtg gcctgggttt tacaggaagaaattgtcccc 60 aaacttatat tgttgcatcc aaaaacagaa ctgcaataat acagaatatgattcttaaaa 120 gtagctctca cagacactgt attaacatat tcctgttcta tcattcacagagttctgttg 180 gagatcagta tatgtaatat ggaaaggacc aacgattcca cgtcgacagaatttttcctg 240 gtagggcttt ctgcccaccc aaagctccag acagttttct tcgttctaattttgtggatg 300 tacctgatga tcctgcttgg aaatggagtc cttatctcag ttatcatctttgattctcac 360 ctgcacaccc ccatgtattt cttcctctgt aatctttcct tcctcgacgtttgctacaca 420 agttcctctg tcccactaat tcttgccagc tttctggcag taaagaaaaaggtttccttc 480 tctgggtgta tggtgcaaat gtttatttct tttgccatgg gggccacggagtgcatgatc 540 ttaggcacga tggcactgga ccgctatgtg gccatctgct acccactgagataccctgtc 600 atcatgagca agggtgccta tgtggccatg gcagctgggt cctgggtcactgggcttgtg 660 gactcagtag tgcagacagc ttttgcaatg cagttaccat tctgtgctaataatgtcatt 720 aaacattttg tctgtgaaat tctggctatc ttgaaactgg cctgtgctgatatttcaatc 780 aatgtgatta gtatgacagg gtcgaatctg attgttctgg ttattccattgttagtaatt 840 tccatctctt acatatttat tgttgccact attctgagga ttccttccactgaaggaaaa 900 cataaggcct tctccacctg ctcagcccac ctgacagtgg tgattatattctatggaacc 960 atcttcttca tgtacgcaaa gcctgagtct aaagcctctg ttgattcaggtaatgaagac 1020 atcattgagg ccctcatctc ccttttctat ggagtgatga ctcccatgcttaatcctctc 1080 atctatagtc tgcgaaacaa ggatgtaaag gctgctgtca aaaacatactgtgtaggaaa 1140 aacttttctg atggaaaatg aatactgatt tatactacat gacttaatattcaatgctgc 1200 tgcagacata aaattcagaa agataaaatt accatgtgaa aacaaattttgccatgtggc 1260 attcaaaacc atatggtaga aatatttttg ggccaggcac a 1301 811201 DNA Homo sapiens misc_feature Incyte ID No 7477940CB1 81 gtaagtttgacttttttaga ttccacatat taagtgacat catttgatat ttgtctttct 60 gtgcctggcttatttcactt aatacaatgt ccttgaggtg ttgctgcaaa tgacaggatt 120 tttttctttatttagattac aaacaaagtc tgaaacctga ggcaatggac ccacagaact 180 attccttggtgtcagaattt gtgttgcatg gactctgcac ttcacgacat cttcaaaatt 240 ttttctttatatttttcttt ggggtctatg tggccattat gctgggtaac cttctcattt 300 tggtcactgtaatttctgat ccctgcctgc actcctcccc tatgtacttc ctgctgggga 360 acctagctttcctggacatg tggctggcct catttgccac tcccaagatg atcagggatt 420 tccttagtgatcaaaaactc atctcctttg gaggatgtat ggctcaaatc ttcttcttgc 480 actttactggtggggctgag atggtgctcc tggtttccat ggcctatgac agatatgtgg 540 ccatatgcaaacccttgcat tacatgactt tgatgagttg gcagacttgc atcaggctgg 600 tgctggcttcatgggtcgtt ggatttgtgc actccatcag tcaagtggct ttcactgtaa 660 atttgccttactgtggcccc aatgaggtag acagcttctt ctgtgacctc cctctggtga 720 tcaaacttgcctgcatggac acctatgtct tgggtataat tatgatctca gacagtgggt 780 tgctttccttgagctgtttt ctgctcctcc tgatctccta caccgtgatc ctcctcgcta 840 tcagacagcgtgctgccggt agcacatcca aagcactctc cacttgctct gcacatatca 900 tggtagtgacgctgttcttt ggcccttgca tttttgttta tgtgcggcct ttcagtaggt 960 tctctgtggacaagctgctg tctgtgtttt ataccatttt tactccactc ctgaacccca 1020 ttatctacacattgagaaat gaggagatga aagcagctat gaagaaactg caaaaccgac 1080 gggtgacttttcaatgaaat ccagccttcc atagtgttag atgtttctat tcattcagca 1140 gatataatttctttaatata attctgctca aagatttcat tctgacacta cattgatata 1200 a 1201 821123 DNA Homo sapiens misc_feature Incyte ID No 7477944CB1 82 catattacagtggagaagtt taacaaattt aaagatgtat taataaaaat tgttttcttt 60 tcaggtaatgtaattaacca tcatttgaaa tacatggcga atagaaacaa tgtgacagag 120 tttattctattggggcttac agagaatcca aaaatgcaga aaatcatatt tgttgtgttt 180 tctgtcatctacatcaacgc catgatagga aatgtgctca ttgtggtcac catcactgcc 240 agcccatcactgagatcccc catgtacttt ttcctggcct atctctcctt tattgatgcc 300 tgctattcctctgtcaatac ccctaagctg atcacagatt cactctatga aaacaagact 360 atcttattcaatggatgtat gactcaagtc tttggagaac attttttcag aggtgttgag 420 gtcatcctacttactgtaat ggcctatgac cactatgtgg ccatctgcaa gcccttgcac 480 tataccaccatcatgaagca gcatgtttgt agcctgctag tgggagtgtc atgggtagga 540 ggctttcttcatgcaaccat acagatcctc ttcatctgtc aattaccttt ctgtggtcct 600 aatgtcatagatcactttat gtgtgatctc tacactttga tcaatcttgc ctgcactaat 660 acccacactctaggactctt cattgctgcc aacagtgggt tcatatgcct gttaaactgt 720 ctcttgctcctggtctcctg cgtggtcata ctgtactcct taaagaccca cagcttagag 780 gcaaggcatgaagccctctc tacctgtgtc tcccacatca cagttgtcat cttatccttt 840 ataccctgcatatttgtgta catgagacct ccagctactt tacccattga taaagcagtt 900 gctgtattctacactatgat aacttctatg ttaaacccct taatctacac cttgaggaat 960 gctcaaatgaaaaatgccat taggaaattg tgtagtagga aagctatttc aagtgtcaaa 1020 taaatgtgactggagcccaa caagattcaa ctgaggcaag ggtcaaaagg acattttggg 1080 taatgccagcaaggaatact tatttgataa ataaaataat taa 1123 83 2053 DNA Homo sapiensmisc_feature Incyte ID No 7480405CB1 83 ctgaaggagc actatggtta tagctggctctcgtcgtggc gatactatta tcaatggatg 60 tggccactgc tcaggtgacc gaacaaactcggtcgtatgg ttgtatcgca cgatgagatt 120 gtctatgatg gcagtcgtcg tatgtgtatggcatcgtcat agactgttgc gctttgacgt 180 tgaccacccg gtggcttcaa cgcggttttatcccgtttga aaggtagttg gcggaaaaag 240 gatggcacat accaaagcaa aaggtggtggccccatagtg ggagtatacc tgtgttctgg 300 ctccctcacg taaacgtctt gcgaagtctaaaggggtcac agtggtgttg ttgaggacct 360 tccctgctca tgagaatgtg agctcgctccacgcatcaca gagcctcaca gcatggcctg 420 atcctatggg aggaggaggt tcaaacatctggcataattt tttttccaag ttacgcttta 480 gttacttgct aaatctttct tatatcatatatacctctga gtattttgaa gatgcctatt 540 gtttcttaaa ccagcgatgt tgattcaattcagctgtcta tgacaaaaac tctacaataa 600 ggagtttgct ttatctttct ttcaatgagtcactgtttgt gttagcagag gagggaggtt 660 ctgcaaattt tcagtacttg ttgataaatggcattatcat caggaaagtt tatgaatttg 720 aaccgtgaca accttactat cagttaccaattcttctggc ctatagttgt gaattcttag 780 tttgttttgt gaatttgtta tatgtcatttatatactcaa atccccagac ccacgggact 840 caggttagca caatgagcat acacaaatgtgagtactcac gaaacactca ttacaaaggg 900 acgcgttaca ctgactccaa aactctccttggtggcctag gtgaaacctc atggccaaca 960 tcaccaggat ggccaaccac actggaaagttggatttcat cctcatggga ctcttcagac 1020 gatccaaaca tccagctcta cttagtgtggtcatctttgt ggttttcctg aaggcgttgt 1080 ctggaaatgc tgtcctgatc cttctgatacactgtgacgc ccacctccac agccccatgt 1140 actttttcat cagtcaattg tctctcatggacatggcgta catttctgtc actgtgccca 1200 agatgctcct ggaccaggtc atgggtgtgaataaggtctc agcccctgag tgtgggatgc 1260 agatgttcct ctatctgaca ctagcaggttcggaattttt ccttctagcc accatggcct 1320 atgaccgcta cgtggccatc tgccatcctctccgttaccc tgtcctcatg aaccataggg 1380 tctgtctttt cctggcatcg ggctgctggttcctgggctc agtggatggc ttcatgctca 1440 ctcccatcac catgagcttc cccttctgcagatcctggga gattcatcat ttcttctgtg 1500 aagtccctgc tgtaacgatc ctgtcctgctcagacacctc actctatgag accctcatgt 1560 acctatgctg tgtcctcatg ctcctcatccctgtgacgat catttcaagc tcctatttac 1620 tcatcctcct caccgtccac aggatgaactcagcagaggg ccggaaaaag gcctttgcca 1680 cctgctcctc ccacctgact gtggtcatcctcttctatgg ggctgccgtc tacacctaca 1740 tgctccccag ctcctaccac acccctgagaaggacatgat ggtatctgtc ttctatacca 1800 tcctcactcc ggtgctgaac cctttaatctatagtcttag gaataaggat gtcatggggg 1860 ctctgaagaa aatgttaact gtgagattcgtcctttagga aattataaag taggaaattt 1920 ggatataaag atttattttc cttttctctacccatcagat acttaggatt ttatccctgt 1980 tattccttag actctcatac aatgatgcctcatctcatat tcatctcatt ttgaggaatt 2040 ctttcactgt gtg 2053 84 939 DNAHomo sapiens misc_feature Incyte ID No 7482486CB1 84 atgcggctggccaaccagac cctgggtggt gactttttcc tgttgggaat cttcagccag 60 atctcacaccctggccgcct ctgcttgctt atcttcagta tatttttgat ggctgtgtct 120 tggaatattacattgatact tctgatccac attgactcct ctctgcatac tcccatgtac 180 ttctttataaaccagctctc actcatagac ttgacatata tttctgtcac tgtccccaaa 240 atgctggtgaaccagctggc caaagacaag accatctcgg tccttgggtg tggcacccag 300 atgtacttctacctgcagtt gggaggtgca gagtgctgcc ttctagccgc catggcctat 360 gaccgctatgtggctatctg ccatcctctc cgttactctg tgctcatgag ccatagggta 420 tgtctcctcctggcatcagg ctgctggttt gtgggctcag tggatggctt catgctcact 480 cccatcgccatgagcttccc cttctgcaga tcccatgaga ttcagcactt cttctgtgag 540 gtccctgctgttttgaagct ctcttgctca gacacctcac tttacaagat tttcatgtac 600 ttgtgctgtgtcatcatgct cctgatacct gtgacggtca tttcagtgtc ttactactat 660 atcatcctcaccatccataa gatgaactca gttgagggtc ggaaaaaggc cttcaccacc 720 tgctcctcccacattacagt ggtcagcctc ttctatggag ctgctattta caactacatg 780 ctccccagctcctaccaaac tcctgagaaa gatatgatgt catccttttt ctacactatc 840 cttacacctgtcttgaatcc tatcatttac agtttcagga ataaggatgt cacaagggct 900 ttgaaaaaaatgctgagcgt gcagaaacct ccatattaa 939 85 930 DNA Homo sapiens misc_featureIncyte ID No 7482535CB1 85 atgacactag gaaacagcac tgaagtcact gaattctatcttctgggatt tggtgcccag 60 catgagtttt ggtgtatcct cttcattgta ttccttctcatctatgtgac ctccataatg 120 ggtaatagtg gaataatctt actcatcaac acagattccagatttcaaac actcacgtac 180 ttttttctac aacatttggc ttttgttgat atctgttacacttctgctat cactcccaag 240 atgctccaaa gcttcacaga agaaaagaat ttgatattatttcagggctg tgtgatacaa 300 ttcttagttt atgcaacatt tgcaaccagt gactgttatctcctggctat gatggcagtg 360 gatccttatg ttgccatctg taagcccctt cactatactgtaatcatgtc ccgaacagtc 420 tgcatccgtt tggtagctgg ttcatacatc atgggctcaataaatgcctc tgtacaaaca 480 ggttttacat gttcactgtc cttctgcaag tccaatagcatcaatcactt tttctgtgat 540 gttcccccta ttcttgctct ttcatgctcc aatgttgacatcaacatcat gctacttgtt 600 gtctttgtgg gatctaactt gatattcact gggttggtcgtcatcttttc ctacatctac 660 atcatggcca ccatcctgaa aatgtcttct agtgcaggaaggaaaaaatc cttctcaaca 720 tgtgcttccc acctgaccgc agtcaccatt ttctatgggacactctctta catgtatttg 780 cagtctcatt ctaataattc ccaggaaaat atgaaagtggcctttatatt ttatggcaca 840 gttattccca tgttaaatcc tttaatctat agcttgagaaataaggaagt aaaagaagct 900 ttaaaagtga tagggaaaaa gttattttaa 930 86 1301DNA Homo sapiens misc_feature Incyte ID No 7482770CB1 86 agacagttctccctctattg cccaggctgg agtgcagtgg tgtaaacata gctccctgca 60 gttgcaaattcctgggctca agtgatcctt ccatctcagc ctcccgagta gctgggacta 120 caggtgtccaccaccatgcc tggctaatga cctcttcttt tgtagataca tcagctacat 180 ggaagcaggaaaccaaacag gatttttaga gtttatcctt ctcggactct ctgaggatcc 240 agaactacagccgttcatat ttgggctgtt cctgtccatg tacctggtga cggtgctggg 300 aaacctgctcatcatcctgg ccatcagctc tgactcccac ctccacaccc ccatgtactt 360 cttcctctccaacctgtcct gggttgacat ctgtttcagc acttgcatcg tccccaagat 420 gctggtgaacatccagaccg agaacaaagc catctcctac atggactgcc tcacacaggt 480 ctatttctccatgttttttc ctattctgga cacgctactc ctgaccgtga tggcctatga 540 ccggtttgtggctgtctgcc accctctgca ctatatgatc atcatgaacc cccacctctg 600 tggcctcctggtttttgtca cctggctcat tggtgtcatg acatccctcc tccatatttc 660 tctgatgatgcatctaatct tctgtaaaga ttttgaaatt ccacattttt tctgcgaact 720 gacgtacatcctccagctgg cctgctctga taccttcctg aacagcacgt tgatatactt 780 tatgacgggtgtgctgggcg tttttcccct ccttgggatc attttctctt attcacgaat 840 tgcttcatccataaggaaga tgtcctcatc tgggggaaaa caaaaagcac tttccacctg 900 tgggtctcacctctccgtcg tttctttatt ttatgggaca ggcattgggg tccacttcac 960 ttctgcggtgactcactctt cccagaaaat ctccgtggcc tcggtgatgt acactgtggt 1020 cacccccatgttgaacccct tcatctacag cctgaggaac aaggatgtga agggagccct 1080 ggggagtctcctcagcaggg cagcctcttg tttgtgatgg atcccttggc cccaggacta 1140 agaagttttgtgagcaccaa tggcaaaaat gttttatttt gaaattctta ctctttaaaa 1200 ttaaaaacatttttttatac tttgagagta caaatgcaga tttcttaaca tgcatttgca 1260 taagggtgaagtctgagctt ttggcgtacc aattacctga a 1301 87 1201 DNA Homo sapiensmisc_feature Incyte ID No 7475695CB1 87 aagataaaaa agcagaaacc tcctattgtgataaatttgc tggtggtggg ctctatcaat 60 acaaataacc atagactagt gcttgtgtcatggaaggaac tgactttgtc tgtgcccaca 120 gccagtcatg accaccataa ttctggaagtagataatcat acagtgacaa cacgtttcat 180 tcttctgggg tttccaacac gaccagccttccagcttctc tttttctcca ttttcctggc 240 aacctatctg ctgacactgc tggagaatcttcttatcatc ttagctatcc acagtgatgg 300 gcagctgcat aagcccatgt acttcttcttgagccacctc tccttcctgg agatgtggta 360 tgtcacagtc atcagcccca agatgcttgttgacttcctc agtcatgaca agagtatttc 420 cttcaatggc tgcatgactc aactttacttttttgtgacc tttgtctgca ctgagtacat 480 ccttcttgct atcatggcct ttgaccgctatgtagccatt tgtaatccac tacgctaccc 540 agtcatcatg accaaccagc tctgtggcacactggctgga ggatgctggt tctgtggact 600 catgactgcc atgattaaga tggtttttatagcacaactt cactactgtg gcatgcctca 660 gatcaatcac tacttttgtg atatctctccactccttaac gtctcctgtg aggatgcctc 720 acaggctgag atggtggact tcttcttggccctcatggtc attgctattc ctctttgtgt 780 tgtggtggca tcctacgctg ctatccttgccaccatcctc aggatccctt ctgctcaggg 840 ccgccaaaag gcattctcca cctgtgcctcccacctgacc gtcgtaattc tcttctattc 900 catgacactt ttcacctatg cccgtcccaaactcatgtat gcctacaatt ccaacaaagt 960 ggtatctgtt ctctacactg tcattgttccactcctcaac cccatcattt actgtctgag 1020 gaaccatgaa gtaaaggcag ccctcagaaagaccatacat tgcagaggaa gtgggcccca 1080 gggaaatggg gctttcagta gttaaaaaatgtatagattc ctttcaggct tgaactgaga 1140 gatgatcact acacactttc cccctcagtcttgtctttgg ttatccccca atctccagta 1200 c 1201 88 1201 DNA Homo sapiensmisc_feature Incyte ID No 7477365CB1 88 atttaagtac agggtaaccc taaatgtcccatgctgttct ggatactgga tcatgaagga 60 atcattcctt ttccatcaga gtaatatcttgttctgcaac taaggaatta tatatacctg 120 agtaaaaatg agaggctgga atcatacaggtgcaaaggaa ttcctcctgg tagggttaac 180 tgaaaatcct aatttgcaga tcccactctttttgcttgtc actctgattt atttcatcac 240 tttgttggat aatttgggta taattattttaatctggtta aatgcccaac ttcatactcc 300 aatgtacttc ttccttggca acctctccttttgtgatatc tgctactcta ctgtctttgc 360 tcctaagatg ctagtcaatt tcctatcaaaacataagtcc agtacatttt ctggctgtgt 420 tctacagagt ttcccttttg cagtatatgtaaccacaaag gacattctcc tgtccatgat 480 ggcttatgac cattacgtgg ccatagctaatcccttgttg tatacagtca ttatggccca 540 aaaagtttgt attcagatgg tccttgcttcttacttaggt gggctcatta attccctgac 600 acacacaata ggtttgctca aattagacttctgtggtcct aatattgtga atcattattt 660 ctgtgatgtt cctcctcttc tgaggctttcttgctctgat gctcatatca atgaaatgct 720 gcccttggtc ttctctgggc tcattgcaatgttcactttc attgtcatta tggtgtctta 780 tatctgcatc atcattgcca tccagagaatccatgcagct gagggaaggt acaaagcctt 840 ctccacttgt gtctcccacc taaccacggtgaccttattc tatgggtctg tttcttttag 900 ttatatccag ccaagttctc agtattccttggaacaggag aaggtcttgg ctgtgtttta 960 tacactggtg atccccatgc taaacccacttatttatagc ctgagaaata aggatgtaaa 1020 agatgcagcc aaaaggttga tatggtgggggaaaaacccc acttgactca gtcctgcata 1080 tagctttgtt aacctaacat ttacctgcaaatatatggcc tatctttaaa atgatatcaa 1140 acaattataa ataaaactat actccagatgctcttgtaca gtttggatca ggaatgatga 1200 g 1201 89 1355 DNA Homo sapiensmisc_feature Incyte ID No 7479899CB1 89 tttccacatt ttttgattaa gaaaactccattcctaagta aatgttttga actgtttctc 60 aaaattcagc atctatcaaa aacatctacaaggcttgtga aagaataaac tgtcggttct 120 catccccaga gtttatcagc aagaagtctggggaggggag caagattttg cgtttctgtc 180 atgttctcga gtgatgccga tgcagctgctgcttacagat tttattatct tttccatcag 240 attcatcatc aacagcatgg aagcgagaaaccaaacagct atttcaaaat tccttctcct 300 gggactgata gaggatccgg aactgcagcccgtccttttc agcctgttcc tgtccatgta 360 cttggtcacc atcctgggga acctgctcatcctcttggct gtcatctctg actctcacct 420 ccacaccccc atgtacttct tcctctccaatctctccttt ttggacattt gtttaagcac 480 aaccacgatc ccaaagatgc tggtgaacatccaagctcag aatcggagca tcacgtactc 540 aggctgcctc acccagatct gctttgtcttgttttttgct ggcttggaaa attgtctcct 600 tgcagcaatg gcctatgacc gctatgtggccatttgtcac ccccttagat acacagtcat 660 catgaacccc cgcctctgtg gcctgctgattcttctctct ctgttgacta gtgttgtgaa 720 tgcccttctt ctcagcctga tggtgttgaggctgtccttc tgcacagacc tggaaatccc 780 gctcttcttc tgtgaactgg ctcaggtcatccaactcacc tgttcagaca ccctcatcaa 840 taacatcctg atatattttg cagcttgcatatttggtggt gttcctctgt ctggaatcat 900 tttgtcttac actcagatca cctcctgtgttttgagaatg ccatcagcaa gtggaaagca 960 caaagcagtt tccacctgtg ggtctcacctctccattgtt ctcttgttct atggggcagg 1020 tttgggggtg tacattagtt ctgtggttactgactcacct aggaagactg cagtggcttc 1080 agtgatgtat tctgtgttcc ctcaaatggtgaaccccttt atctatagtc tgaggaataa 1140 ggacatgaaa ggaaccttga ggaagttcatagggaggata ccttctcttc tgtggtgtgc 1200 catttgcttt ggattcaggt ttctagagtaagtcaaagtg acaggattcc tggtgagcta 1260 gaatgcctga ctctttgttt tgttttgtttttttctctga gatggagtct ttctctgtct 1320 cccaggctgg agtgcaatgg cacgacctcggctca 1355 90 1501 DNA Homo sapiens misc_feature Incyte ID No 7480412CB190 cagtttccag gacttgttta taacagacac tctcatcggg aaatctcatg actcagaact 60gtggcaactt cactacaaat cacccttttg atccacagtt gtgaattctt agttcctggt 120aaattttttg aattgcagat aatttataac acccaaatct acaggcccat gggcctttct 180ttggttagaa cacacacaca cacacacaat ttgtttcaga ggctcaaatt actttaaccc 240caagctttcc tttgtggcct aggtgaaacc tcatggacaa catcacctgg atggccagcc 300acactggatg gtcggatttc atcctgatgg gactcttcag acaatccaaa catccaatgg 360ccaatatcac ctggatggcc aaccacactg gatggtcgga tttcatcctg ttgggactct 420tcagacaatc caaacatcca gcactacttt gtgtggtcat ttttgtggtt ttcctgatgg 480cgttgtctgg aaatgctgtc ctgatccttc tgatacactg tgacgcccac ctccacaccc 540ccatgtactt tttcatcagt caattgtctc tcatggacat ggcgtacatt tctgtcactg 600tgcccaagat gctcctggac caggtcatgg gtgtgaataa gatctcagcc cctgagtgtg 660ggatgcagat gttcttctac gtgacactag caggttcaga atttttcctt ctagccacca 720tggcctatga ccgctacgtg gccatctgcc atcctctccg ttaccctgtc ctcatgaacc 780atagggtgtg tctcttcctg tcatcaggct gctggttcct gggctcagtg gatggcttca 840cattcactcc catcaccatg accttcccct tccgtggatc ccgggagatt catcatttct 900tctgtgaagt tcctgctgta ttgaatctct cctgctcaga cacctcactc tatgagattt 960tcatgtactt gtgctgtgtc ctcatgctcc tcatccctgt ggtgatcatt tcaagctcct 1020atttactcat cctcctcacc atccacggga tgaactcagc agagggccgg aaaaaggcct 1080ttgccacctg ctcctcccac ctgactgtgg tcatcctctt ctatggggct gccatctaca 1140cctacatgct ccccagctcc taccacaccc ctgagaagga catgatggta tctgtcttct 1200ataccatcct cactccagtg gtgaaccctt taatctatag tcttaggaat aaggatgtca 1260tgggggctct gaagaaaatg ttaacagtgg aacctgcctt tcaaaaagct atggagtaga 1320ccattttgag agtaatttac ttttccttct ctctgcactt cacatatgag aatgttatac 1380cagtgttatt tcccagactc caagactgcc atggtgtttg atctcatttt cacacctctt 1440ttagaaatcg ctttcctgta ctagaaactt ttcaatttac actccgtctc acttcaaaat 1500 g1501 91 1301 DNA Homo sapiens misc_feature Incyte ID No 7485460CB1 91aacaagtaat tacaatactg gaataaagca aaaaaatggc atgctgattg atctcagtag 60tcctccctcc atttatcatt ctgattctgc cttttcattt ctacagggca gctacataat 120tcccaatgga gaacaacaca gaggtgactg aattcatcct tgtggggtta actgatgacc 180cagaactgca gatcccactc ttcatagtct tccttttcat ctacctcatc actctggttg 240ggaacctggg gatgattgaa ttgattctac tggactcctg tctccacacc cccatgtact 300tcttcctcag taacctctcc ctggtggact ttggttattc ctcagctgtc actcccaagg 360tgatggtggg gtttctcaca ggagacaaat tcatattata taatgcttgt gccacacaat 420tcttcttctt tgtagccttt atcactgcag aaagtttcct cctggcatca atggcctatg 480accgctatgc agcattgtgt aaacccctgc attacaccac caccatgaca acaaatgtat 540gtgcttgcct ggccataggc tcctacatct gtggtttcct gaatgcatcc attcatactg 600ggaacacttt caggctctcc ttctgtagat ccaatgtagt tgaacacttt ttctgtgatg 660ctcctcctct cttgactctc tcatgttcag acaactacat cagtgagatg gttatttttt 720ttgtggtggg attcaatgac ctcttttcta tcctggtaat cttgatctcc tacttattta 780tatttatcac catcatgaag atgcgctcac ctgaaggacg ccagaaggcc ttttctactt 840gtgcttccca ccttactgca gtttccatct tttatgggac aggaatcttt atgtacttac 900gacctaactc cagccatttc atgggcacag acaaaatggc atctgtgttc tatgccatag 960tcattcccat gttgaatcca ctggtctaca gcctgaggaa caaagaggtt aagagtgcct 1020ttaaaaagac tgtagggaag gcaaaggcct ctataggatt catattttaa ttataaagaa 1080ttcacaataa gataattttt tccacctcat attaatcttt gtctaccaag cccaatattt 1140gggcttcctc atggacagtt tctattgact gttttcttaa acatatgaat tggccatact 1200ttcttcattc tttaagtgac actttttttg ttgttaaaat ctggacattt taaataataa 1260aaaatagcat attctaaaaa tcagatctct cctcccatct a 1301 92 1401 DNA Homosapiens misc_feature Incyte ID No 7472173CB1 92 cacagccacg tttacgtacataagttggta tacacactat gcattgaaaa tagttatatg 60 aataattgac aagaagcaaccacatttcac atgattattc tcatagttgt ataagggtga 120 aaaaacactt tgcattcatcaagtgttttt aatacattca aagtccatta gaagctggtt 180 ttgctgacaa aagaaccagccaaatcatca gtaaagaagg ggtggccagt gcgtatttgt 240 atgtgggtga gggaggacctgaaatagagt caggtcccga aggaccttac atagtcagaa 300 tcctccttat tttttgtcccaactataatc aactgtgctc taagattcta aggagctttc 360 ttgcttgtct ttctagggtatcaagggaca tgagaaatgg cacagtaatc acagaattca 420 tcctgctagg ctttcctgttatccaaggcc tacaaacacc tctctttatt gcaatctttc 480 tcacctacat attaacccttgcaggcaatg ggcttattat tgccactgtg tgggctgagc 540 ccaggctaca aattccaatgtacttcttcc tttgtaactt gtctttctta gaaatctggt 600 acaccaccac agtcatccccaaactgctag gaacctttgt agtggcaaga acagtaatct 660 gcatgtcctg ctgcctgctgcaggccttct tccacttctt cgtgggcacc accgagttct 720 tgatcctcac tatcatgtcttttgaccgct acctcaccat ctgcaatccc cttcaccacc 780 ccaccatcat gaccagcaaactctgcctgc agctggccct gagctcctgg gtggtgggct 840 tcaccattgt cttttgtcagacgatgctgc tcatccagtt gccattctgt ggcaataatg 900 ttatcagtca tttctactgtgatgttgggc ccagtttgaa agccgcctgc atagacacca 960 gcattttgga actcctgggcgtcatagcaa ccatccttgt gatcccaggg tcacttctct 1020 ttaatatgat ttcttatatctacattctgt ccgcaatcct acgaattcct tcagccactg 1080 gccaccaaaa gactttctctacctgtgcct cgcacctgac agttgtctcc ctgctctacg 1140 gggctgttct gttcatgtacctaagaccca cagcacactc ctcctttaag attaataagg 1200 tggtgtctgt gctaaatactatcctcaccc cccttctgaa tccctttatt tatactatta 1260 gaaacaagga ggtgaagggagccttaagaa aggcaatgac ttgcccaaag actggtcatg 1320 caaagtaaaa catgcaacacatcaaagtga gcttaatgca gataaaaaca atgaaagttg 1380 agagaggatt ttggagaagt t1401 93 1116 DNA Homo sapiens misc_feature Incyte ID No 7475690CB1 93aattgatacc cttgtcaact tgtgtgaata gaaaaaacac taagtgatga ttttcccttc 60tcatgatagt caggctttca cctccgtgga catggaagtg ggaaattgca ccatcctgac 120tgaattcatc ttgttgggtt tctcagcaga ttcccagtgg cagccgattc tatttggagt 180gtttctgatg ctctatttga taaccttgtc aggaaacatg accttggtta tcttaatccg 240aactgattcc cacttgcata cacctatgta ctttttcatt ggcaatctgt cttttttgga 300tttctggtat acctctgtgt atacccccaa aatcctggcc agttgtgtct cagaagataa 360gcgcatttcc ttggctggat gtggggctca gctgtttttt tcctgtgttg tagcctacac 420tgaatgctat ctcctggcag ccatggcata tgaccgccat gcagcaattt gtaacccatt 480gctttattca ggtaccatgt ccaccgccct ctgtactggg cttgttgctg gctcctacat 540aggaggattt ttgaatgcca tagcccatac tgccaataca ttccgcctgc atttttgtgg 600taaaaatatc attgaccact ttttctgtga tgcaccacca ttggtaaaaa tgtcctgtac 660aaacaccagg gtctacgaaa aagtcctgct tggtgtggtg ggcttcacag tactctccag 720cattcttgct atcctgattt cctatgtcaa catcctcctg gctatcctga gaatccactc 780agcttcagga agacacaagg cattctccac ctgtgcttcc cacctcatct cagtcatgct 840cttctatgga tcattgttgt ttatgtattc aaggcctagt tccacctact ccctagagag 900ggacaaagta gctgctctgt tctacaccgt gatcaaccca ctgctcaacc ctctcatcta 960tagcctgaga aacaaagata tcaaagaggc cttcaggaaa gcaacacaga ctatacaacc 1020acaaacatga aggttattct ctttgcaaat gctgttattg aattttccag attattggct 1080tataaatgtg ttcatttgca tttctgtagt tcaatt 1116 94 1352 DNA Homo sapiensmisc_feature Incyte ID No 7476068CB1 94 attacttgga gatattgtct ggctgtcattcattagagta tagaccacac ctttcatatt 60 tgcatgtttg ttatttacat gttcaaagaagacgaagatt atggaatatg ccataagctc 120 ctggtgacat cgcaaagaat gtgcagattttatcttcttt ctacctctgt gagtagaagg 180 tgaggttctg anagttctcc ccagctatgcctactgtaaa ccacagtggc actagccaca 240 cagtcttcca cttgctgggc atccctggcctacaggacca gcacatgtgg atttctatcc 300 cattcttcat ttcctatgtc accgcccttcttgggaacag cctgctcatc ttcattatcc 360 tcacaaagcg cagcctccat gaacccatgtacctcttcct ctgcatgctg gctggagcag 420 acattgtcct ctccacgtgc accattcctcaggccttagc tatcttctgg ttccgtgctg 480 gggacatctc cctggatcgt tgcatcactcagctcttctt catccattcc accttcatct 540 ctgagtcagg gatcttgctg gtgatggcctttgaccacta tattgccata tgctacccac 600 tgaggtacac caccattctt acaaatgctctgatcaagaa aatttgtgtg actgtctctc 660 tgagaagtta tggtacaatt ttccctatcatatttctttt aaaaagattg actttctgcc 720 agaataatat tattccacac accttttgtgaacacattgg cctagccaaa tatgcatgta 780 atgacattcg aataaacatt tggtatgggttttccattct aatgtcgacg gtggtcttag 840 atgttgtact aatttttatt tcctatatgctgattctcca tgctgtcttc cacatgcctt 900 ctccagatgc ttgccacaaa gctctcaacacatttggctc ccatgtctgc atcatcatcc 960 tcttttatgg gtctggcatc ttcacaatccttacccagag gtttggacgc cacattccac 1020 cttgtatcca catcccgttg gctaatgtctgcattctggc tccacctatg ctgaatccca 1080 ttatttatgg gatcaaaacc aagcaaatccaggaacaggt ggttcagttt ttgtttataa 1140 aacagaaaat aactttggtt taagaactgagttttcagaa tctctagcta tctggtaagt 1200 gggtatgaaa gtggtagatg ggagaggtcagctgataccg taggaaataa ctcagtgagt 1260 acgatgtctg gagcaaggtc aactgggaagttacagggct tattcttcca ttttttaacc 1320 accttaggaa agcaatgcaa tgtttgactgac 1352 95 1101 DNA Homo sapiens misc_feature Incyte ID No 7476163CB1 95tttgaaaacc atatccaaat tagatgacat tatcaatatt atttaactgc actattattt 60cttccagaga tgaacctgat aaaggatctg tgattcaatg gatcagagaa attacaccag 120agtgaaagaa tttaccttcc tgggaattac tcagtcccga gaactgagcc aggtcttatt 180taccttcctg tttttggtgt acatgacaac tctaatggga aacttcctca tcatggttac 240agttacctgt gaatctcacc ttcatacgcc catgtacttc ctgctccgca acctgtctat 300tcttgacatc tgcttttcct ccatcacagc tcctaaggtc ctgatagatc ttctatcaga 360gacaaaaacc atctccttca gtggctgtgt cactcaaatg ttcttcttcc accttctggg 420gggagcagac gttttttctc tctctgtgat ggcgtttgac cgctatatag ccatctccaa 480gcccctgcac tatatgacca tcatgagtag ggggcgatgc acaggcctca tcgtgggctt 540cctgggtggg gggcttgtcc actccatagc gcagatttct ctattgctcc cactccctgt 600ctgtggaccc aatgttcttg acactttcta ctgcgatgtc ccccaggtcc tcaaacttgc 660ctgcactgac accttcactc tggagctcct gatgatttca aataatgggt tagtcagttg 720gtttgtattc ttctttctcc tcatatctta cacggtcatc ttgatgatgc tgaggtctca 780cactggggaa ggcaggagga aagccatctc cacctgcacc tcccacatca ccgtggtgac 840cctgcatttc gtgccctgca tctatgtcta tgcccggccc ttcactgccc tccccacaga 900cactgccatc tctgtcacct tcactgtcat ctcccctttg ctcaatccta taatttacac 960gctgaggaat caggaaatga agttggccat gaggaaactg aagagacggc taggacaatc 1020agaaaggatt ttaattcaat aagggtaaga tagtacccat atttaaagat agacattaaa 1080tttcactttc tcaaaatggg a 1101 96 1201 DNA Homo sapiens misc_featureIncyte ID No 7476166CB1 96 aaatctgaaa aacgtgaaca atgcaacaaa ctgcaaaaactacaaccgca tgggaagttt 60 ctgcactgca ttctaggtgt ttaggaagac aacaaaataaatatcccagt gctttcacat 120 gacatggttt aaaaccaaag agaataaaga ggatgattgaatggagatgg aaaactgcac 180 cagggtaaaa gaatttattt tccttggcct gacccagaatcgggaagtga gcttagtctt 240 atttcttttc ctactcttgg tgtatgtgac aactttgctgggaaacctcc tcatcatggt 300 cactgttacc tgtgaatctc gccttcacac gcccatgtattttttgctcc ataatttatc 360 tattgccgat atctgcttct cttccatcac agtgcccaaggttctggtgg accttctgtc 420 tgaaagaaag accatctcct tcaatcattg cttcactcagatgtttctat tccaccttat 480 tggaggggtg gatgtatttt ctctttcggt gatggcattggatcgatatg tggccatctc 540 caagcccctg cactatgcga ctatcatgag tagagaccattgcattgggc tcacagtggc 600 tgcctggttg gggggctttg tccactccat cgtgcagatttccctgttgc tcccactccc 660 tttctgcgga cccaatgttc ttgacacttt ctactgtgatgtccaccggg tcctcaaact 720 ggcccataca gacattttca tacttgaact actaatgatttccaacaatg gactgctcac 780 cacactgtgg tttttcctgc tcctggtgtc ctacatagtcatattatcat tacccaagtc 840 tcaggcagga gagggcagga ggaaagccat ctccacctgcacctcccaca tcactgtggt 900 gaccctgcat ttcgtgccct gcatctatgt ctatgcccggcccttcactg ccctccccat 960 ggataaggcc atctctgtca ccttcactgt catctcccctctgctcaacc ccttgatcta 1020 cactctgagg aaccatgaga tgaagtcagc catgaggagactgaagagaa gacttgtgcc 1080 ttctgataga aaatagaaaa aaaaatcctc agctcttcatcaccaaagat atcttatatt 1140 tattattttt cccatgaagt catattcata tattcaaatatattgtcaaa ccaactacac 1200 t 1201 97 1301 DNA Homo sapiens misc_featureIncyte ID No 7476686CB1 97 taattgtttc aaagtgatat aatatttaag ctaatctctgtgttgatata tttaaaatta 60 tatgatctca tatcatcaac tattatcacc aactaatagaaataagaaaa tattggtgtt 120 aactgtgact tattttttaa ttctctttgt atataaagaacttctggaac ctttctgagt 180 tgagtaaatg gatcttaaaa atggatctct agtgaccgagtttattttac taggattttt 240 tggacgatgg gaacttcaaa ttttcttctt tgtgacattttccctgatct acggtgctac 300 tgtgatggga aacattctca ttatggtcac agtgacatgtaggtcaaccc ttcattctcc 360 cttgtacttt ctccttggaa atctctcttt tttggacatgtgtctctcca ctgccacaac 420 acccaagatg atcatagatt tgctcactga ccacaagaccatctctgtgt ggggctgcgt 480 gacccagatg ttcttcatgc acttctttgg gggtgctgagatgactcttc tgataatcat 540 ggcctttgac aggtatgtag ccatatgtaa acccctgcactataggacaa tcatgagcca 600 caagctgcta aaggggtttg cgatactttc atggataattggttttttac actccataag 660 ccagatagtt ttaacaatga acttgccttt ctgtggccacaatgtcataa acaacatatt 720 ttgtgatctt ccccttgtga tcaagcttgc ttgcattgaaacatacaccc tggaattatt 780 tgtcattgct gacagcgggc tgctctcttt cacctgtttcatcctcttgc ttgtttctta 840 cattgtcatc ctggtcagtg taccaaaaaa atcatcacatgggctctcca aggcgctgtc 900 cacattgtct gcccacatca ttgtggtcac tctgttctttggaccttgta tttttatcta 960 tgtttggcca ttcagtagtt tggcaagcaa taaaactcttgccgtatttt atacagttat 1020 cacaccctta ctgaatccga gtatttatac cctgagaaataagaaaatgc aagaggccat 1080 aagaaaatta cggttccaat atgttagttc tgcacagaatttctagatgt tagcactata 1140 taattaactt ttaaatgcta cgataagata gtttgaatagattatgtata atgcatcatt 1200 tcacttttct tatgttataa taataacgca taaagacaatactaaattac tttaaatttt 1260 acatttaaga cttttataaa cataaggata gagatctgca g1301 98 1301 DNA Homo sapiens misc_feature Incyte ID No 7477363CB1 98tcaaaatcaa aatttacaaa aaatgacatc tctgtgattt tactgacctt ctatttgatt 60ccttagaaga gagaataaag atacttttgg ttcatccata actcaagtta actcacatct 120gctgatacta cctaggtcca gtgggaaaaa caagaaaact aagatgttgg agagtaatta 180caccatgcca actgagttcc tatttgttgg attcacagat tatctacctc tcagagtcac 240actgttcttg gtattccttc tggtatatac attaactatg gtcggaaata tactcttaat 300aattctagtt aatattaatt caagccttca aattcccatg tattattttc ttagcaactt 360atctttctta gacatcagct gttctacagc aatcactcct aaaatgctgg caaacttctt 420ggcatccagg aaaagcatct ctccttatgg gtgtgcacta caaatgtttt tcttcgcttc 480ttttgctgat gctgagtgcc ttatcctggc agcaatggct tatgaccgct atgcagccat 540ctgcaaccca ctgctctata ctacactgat gtctaggaga gtctgtgtct gcttcattgt 600gttggcatat ttcagtggaa gtacaacatc actggtccat gtgtgcctca cattcaggct 660gtcattttgt ggctccaata tcgtcaatca ttttttctgt gatatcccac ctcttctggc 720tttatcatgt acagacactc agatcaacca gcttctgctc tttgctttgt gcagcttcat 780ccagaccagc acttttgtgg taatatttat ttcttacttc tgcatcctca tcactgtgtt 840gagcatcaag tcctcaggtg gcagaagcaa aacattctcc acttgtgctt cccacctcat 900agcagtcacc ttattctatg gagcgctcct gtttatgtac ttacagccca ccactagcta 960ttccctagac actgataagg tggtggcagt gttttatact gttgtatttc ccatgtttaa 1020tccaataatt tatagtttca gaaacaagga tgtgaaaaat gctctcaaaa agctattaga 1080aagaattgga tattcaaatg aatggtattt aaatcgttta agaatagtca atatctaact 1140tacccttcca atctcataaa cagcaattat gccatgaaca tcttatgtgt taactatttt 1200aaatttatca cattttcaga aataaagata acttgttata ctcagtgcat taaaatgctt 1260catcctctct tccaaaaatg ttctctccac aattctactc t 1301 99 1152 DNA Homosapiens misc_feature Incyte ID No 7477368CB1 99 gctgccacta aattagtctgtgcaaaaatc ccactttgag tttgattgct atattttttc 60 ctagttctcc tcccaactggaaatgctaga gtccttccag aaatcagagc aaatggcctg 120 gagcaatcag tctgcggtaaccgaattcat actacggggt ctgtccagtt ctttagaact 180 ccagattttc tacttcctgtttttctccat agtctatgca gccactgtgc tggggaacct 240 tcttattgtg gtcaccattgcatcagagcc acaccttcat tcccctatgt actttctgct 300 gggcaatctc tccttcattgacatgtccct ggcctcattt gccaccccca aaatgattgc 360 agacttcctt agagaacacaaagccatctc ttttgaaggc tgcatgaccc agatgttctt 420 cctacatctc ttagggggtgctgagattgt actgctgatc tccatgtcct ttgataggta 480 cgtggctatc tgtaagcctctacattacct aacaatcatg agccgaagaa tgtgtgttgg 540 gcttgtgata ctttcctggattgtcggcat cttccatgct ctgagtcagt tagcatttac 600 agtgaatctg cccttctgtggacccaatga agtagacagt ttcttttgtg acctcccttt 660 ggtgattaaa cttgcttgtgtcgacacata tattctgggg gtgttcatga tctcaaccag 720 tggcatgatt gccctggtgtgcttcatcct cttggtgatc tcttacacta tcatcctggt 780 caccgttcgg cagcgttcctctggtggatc ctccaaagcc ctctccacgt gcagtgccca 840 ctttactgtt gtgacccttttctttggccc atgcactttc atttatgtgt ggcctttcac 900 aaatttccca atagacaaagtactctcagt attttatacc atatacactc ccctcttgaa 960 tccagtgatc tataccgttaggaataaaga tgtcaagtat tccatgagga aactaagcag 1020 ccatatcttt aaatctaggaagactgatca tactccttaa ttttcctcat aggaaaataa 1080 aatacctgtt cagcatttatccccctcatt cagttggtca acatattgat gctattgcaa 1140 gaactcaatt ag 1152 1001408 DNA Homo sapiens misc_feature Incyte ID No 7480408CB1 100tactcgaaag acagaaataa atggtcatga acaaaaagat tgtttgatca tgaactctaa 60atagtaatca ccaaatcaag aaaatcctta aatgaacaat gatggtataa tgagatgtag 120cacaatcctg ctcaggcagt tctctcaggg aaattatgag cttcaagaaa taagatcgac 180ttgaccttgg tttgttcatg actacatcat aatgttttat gtaaatcaga tacctttcca 240actttgtcat atctcttttg tgtaccctac agagctatgg agcagagcaa ttattccgtg 300tatgccgact ttatccttct gggtttgttc agcaacgccc gtttcccctg gcttctcttt 360gccctcattc tcctggtctt tttgacctcc atagccagca acgtggtcaa gatcattctc 420atccacatag actcccgcct ccacaccccc atgtacttcc tgctcagcca gctctccctc 480agggacatcc tgtatatttc caccattgtg cccaaaatgc tggtcgacca ggtgatgagc 540cagagagcca tttcctttgc tggatgcact gcccaacact tcctctactt gaccttagca 600ggggctgagt tcttcctcct aggactcatg tcctatgatc gctacgtagc catctgcaac 660cctctgcact atcctgtcct catgagccgc aagatctgct ggttgattgt ggcggcagcc 720tggctgggag ggtctatcga tggtttcttg ctcacccccg tcaccatgca gttccccttc 780tgtgcctctc gggagatcaa ccacttcttc tgcgaggtgc ctgcccttct gaagctctcc 840tgcacggaca catcagccta cgagacagcc atgtatgtct gctgtattat gatgctcctc 900atccctttct ctgtcatctc gggctcttac acaagaattc tcattactgt ttataggatg 960agcgaggcag aggggagggg aaaggctgtg gccacctgct cctcacacat ggtggttgtc 1020agcctcttct atggggctgc catgtacaca tacgtgctgc ctcattctta ccacacccct 1080gagcaggaca aagctgtatc tgccttctac accatcctta ctcccatgct caatccactc 1140atttacagcc ttaggaacaa ggatgtcaca ggggccctac agaaggttgt ggggaggtgt 1200gtgtcctcag gaaaggtaac cactttctaa agaaatttca tatgctgcta gagacttgaa 1260atgaaggata caagacttta tcattgccct tgaatttaaa tattctctgc ctggaaacaa 1320gtgacccaca tgccaccaac tgtggggcat ttatgggatt tggaaagctg cctgggattt 1380taaggatttc atttttttga aaggtatg 1408 101 1301 DNA Homo sapiensmisc_feature Incyte ID No 7480409CB1 101 taattttgaa caacttctaaacaacagaaa caacaacaaa gcatctgccc aatttgaata 60 taaagaatat tatgtaggttcatagaggac cacttgagtt gccttcaaaa atgtaaggac 120 caacaatgta gattacaactagaaagggat caagactacg atatttaaga accatctttc 180 catcatttga ttcttcgtgagtgttcagga tttctgtttc ccaggtccaa gcttcatcat 240 ccaccgatgc ccaattcaaccaccgtgatg gaatttctcc tcatgaggtt ttctgatgtg 300 tggacactac agattttacattctgcatcc ttctttatgt tgtatttggt aactctaatg 360 ggaaacatcc tcattgtgaccgtcaccacc tgtgacagca gccttcacat gcccatgtac 420 ttcttcctca ggaatctgtctatcttggat gcctgctaca tttctgttac agtccctacc 480 tcatgtgtca attccctactggacagcacc accatttcta aggcgggatg tgtagctcag 540 gtcttcctcg tggttttttttgtatatgtg gagcttctgt ttctcaccat tatggctcat 600 gaccgctatg tggctgtctgccagccactt cactaccctg tgatcgtgaa ctctcgaatc 660 tgcatccaga tgacactggcctccctactc agtggtcttg tctatgcagg catgcacact 720 ggcagcacat tccagctgcccttctgtcgg tccaacgtta ttcatcaatt cttctgtgac 780 atcccctctc tgctgaagctctcttgctct gacaccttca gcaatgaggt catgattgtt 840 gtctctgctc tgggggtaggtggcggctgt ttcatcttta tcatcaggtc ttacattcac 900 atcttttcga ccgtgctcgggtttccaaga ggagcagaca gaacaaaggc cttttccacc 960 tgcatccctc acatcctggtggtgtcagtc ttcctcagtt catgctcttc tgtgtacctc 1020 aggccacctg cgatacctgcagccacccag gatctgatcc tttctggttt ttattccata 1080 atgcctcccc tctttaaccctattatttac agtcttagaa ataagcaaat aaaggtggcc 1140 atcaagaaaa tcatgaagagaattttttat tcagaaaatg tgtaagaaac ccgagaggct 1200 caccctaggc tgttttgtgatattcatgtt ttcaggaata agttgtaata attgattgtg 1260 gttattagat aaaattggtgtaaatttaat aaataaggct a 1301 102 1476 DNA Homo sapiens misc_featureIncyte ID No 7482487CB1 102 catttggtca atgaatcacc cttttttcca actagtatttacttaaccct actatgggct 60 ggataacttt ctggatacaa gaaatgcagc atggacagaacagatatggt taaaacccca 120 ttcttggtgt agcatacagc aattgtatca cgcagttaccataacctcca gcagcatgat 180 gaaccataga cgcaatatag aaggagctgt tctctgacagggaaatgcag ccatggtttt 240 tgcttcatga tgtgcatgtt ggtctgcctg ttcttctctagcctctagcc tggaagcttc 300 atcctgacgg taccctcaga agtgtcacct ctactgcagacctttcccat cttgaccgtg 360 ttctcttgcc tccttcctgg tccttgtgtc ttcccgttgccctgggacgc tcgtgggcca 420 tatcaatgac gaacacatca tcctctgact tcaccctcctggggcttctg gtgaacagtg 480 aggctgccgg gattgtattt acagtgatcc ttgctgttttcttgggggcc gtgactgcaa 540 atttggtcat gatattcttg attcaggtgg actctcgcctccacaccccc atgtactttc 600 tgctcagtca gctgtccatc atggacaccc ttttcatctgtaccactgtc ccaaaactcc 660 tggcagacat ggtttctaaa gagaagatca tttcctttgtggcctgtggc atccagatct 720 tcctctacct gaccatgatt ggttctgagt tcttcctcctgggcctcatg gcctatgact 780 gctacgtggc tgtctgtaac cctctgagat acccagtcctgatgaaccgc aagaagtgtc 840 ttttgctggc tgctggtgcc tggtttgggg gctccctcgatggctttctg ctcactccca 900 tcaccatgaa tgtcccttac tgtggctccc gaagtatcaaccattttttc tgtgagatcc 960 cagcagttct gaaactggcc tgtgcagaca cgtccttgtatgaaactctg atgtacatct 1020 gctgtgtcct catgttgctc atccccatct ctatcatctccacttcctac tccctcatct 1080 tgttaaccat ccaccgcatg ccctctgctg aaggtcgcaaaaaggccttc accacttgtt 1140 cctcccactt gactgtagtt agcatcttct atggggctgccttctacaca tacgtgctgc 1200 cccagtcctt ccacaccccc gagcaggaca aagtagtgtcagccttctat accattgtca 1260 cgcccatgct taatcctctc atctacagcc tcagaaacaaggacgtcata ggggcattta 1320 aaaaggtatt tgcatgttgc tcatctgctc agaaagtagcaacaagtgat gcttagagag 1380 tcactgccca gaggataagg cttcctaagg acttcctccatttgccctgt ttccctggag 1440 atgatctgct cagctatcaa cctacactta ctactg 1476103 1331 DNA Homo sapiens misc_feature Incyte ID No 7485424CB1 103tttgctctcc atcacatttc cagaattcca gtatgctaac aatcattata ttagttaaat 60aaattaataa ataaatctaa ttaattaaac tctttacaat acaataaata taaaaacacc 120acatatagga tttacagtat taaaatatga cttagactta actcttttct ctacttccac 180atttagatgg ccagaaaaga tatggctcac atcaattgca cccaggcgac agagtttatt 240cttgtgggcc tcacagacca tcaggagttg aagatgcccc tctttgtgct attcttatcc 300atctacctct tcacagtggt aggcaacttg ggtttgatcc tactcattag agcggataca 360agtctcaaca caccaatgta cttctttctt agcaacctag cttttgtgga tttctgttac 420tcttctgtca ttacacccaa aatgcttggg aatttcttgt acaaacaaaa tgttatatcc 480tttgatgcat gtgctactca actgggctgc tttctcacct tcatgatatc agaatccttg 540ctactggctt ccatggccta tgaccgatat gtggccattt gtaaccctct attgtatatg 600gttgtaatga ctccaggaat ctgcattcaa cttgtagcag ttccttatag ctatagcttc 660ctaatggcac tatttcacac catcctcacc ttccgcctct cctattgcca ctccaacatt 720gtcaaccatt tctattgtga tgacatgcct ctcctcaggc taacttgctc agacactcgc 780ttcaaacagc tctggatctt tgcctgtgct ggtatcatgt tcatttcctc ccttctgatt 840gtctttgtct cctacatgtt catcatttct gccatcctga ggatgcattc agctgaggga 900agacagaagg ctttctcgac gtgtggctct cacatgctgg cagtcaccat attctatggg 960accctcattt ttatgtactt acagcctagc tctagccatg ccctggacac agacaagatg 1020gcctctgtct tctacacagt gatcattccc atgttgaatc ccttaatcta tagcctccag 1080aataaggagg tgaaagaagc tctgaagaaa atcattatca ataaaaacta gagttttgtg 1140tttataaaat taagaaagta acttgagtaa ggaaaaatgg acttctttca tggtatgatt 1200tttttcccag tataagttat caggatcctt gtttctcaat atgtgatgta tacatatatt 1260ttcgctgtgt aatacaattt tctagagaat ttctcttaga acgttaggta taaaagtaac 1320tataagaatt t 1331 104 966 DNA Homo sapiens misc_feature Incyte ID No7475196CB1 104 atgacaattc ttcttaatag cagcctccaa agagccactt tcttcctgacgggcttccaa 60 ggtctagaag gtctccatgg ctggatctct attcccttct gcttcatctacctgacagtt 120 atcttgggga acctcaccat tctccacgtc atttgtactg atgccactctccatggaccc 180 atgtactatt tcttgggcat gctagctgtc acagacttag gcctttgcctttccacactg 240 cccactgtgc tgggcatttt ctggtttgat accagagaga ttggcatccctgcctgtttc 300 actcagctct tcttcatcca caccttgtct tcaatggagt catcagttctgttatccatg 360 tccattgacc gctacgtggc cgtctgcaac ccactgcatg actccaccgtcctgacacct 420 gcatgtattg tcaagatggg gctaagctca gtgcttagaa gtgctctcctcatcctcccc 480 ttgccattcc tcctgaagcg cttccaatac tgccactccc atgtgctggctcatgcttat 540 tgtcttcacc tggagatcat gaagctggcc tgctctagca tcattgtcaatcacatctat 600 gggctctttg ttgtggcctg caccgtgggt gtggactcac tgctcatctttctctcatac 660 gccctcatcc ttcgcaccgt gctcagcatt gcctcccacc aggagcgactccgagccctc 720 aacacctgtg tctctcatat ctgtgctgta ctgctcttct acatccccatgattggcttg 780 tctcttgtgc atcgctttgg tgaacatctg ccccgcgttg tacacctcttcatgtcctat 840 gtgtatctgc tggtaccacc ccttatgaac cccatcatct acagcatcaagaccaagcaa 900 attcgccagc gcatcattaa gaagtttcag tttataaagt cacttaggtgtttttggaag 960 gattaa 966 105 1101 DNA Homo sapiens misc_feature IncyteID No 7475295CB1 105 gatacagcca aaactaaaat ttagactata taatggagaataatttttaa gtttcttttc 60 ctccaatctc atataaattg gagacatggg caaggaaaactgcaccactg tggctgagtt 120 cattctcctt ggactatcag atgtccctga gttgagagtctgcctcttcc tgctgttcct 180 tctcatctat ggagtcacgt tgttagccaa cctgggcatgattgcactga ttcaggtcag 240 ctctcggctc cacaccccca tgtacttttt cctcagccacttgtcctctg tagatttctg 300 ctactcctca ataattgtgc caaaaatgtt ggctaatatctttaacaagg acaaagccat 360 ctccttccta gggtgcatgg tgcaattcta cttgttttgcacttgtgtgg tcactgaggt 420 cttcctgctg gccgtgatgg cctatgaccg ctttgtggccatctgtaacc ctttgctata 480 cacagtcacc atgtcttgga aggtgcgtgt ggagctggcttcttgctgct acttctgtgg 540 gacggtgtgt tctctgattc atttgtgctt agctcttaggatccccttct atagatctaa 600 tgtgattaac cactttttct gtgatctacc tcctgtcttaagtcttgctt gctctgatat 660 cactgtgaat gagacactgc tgttcctggt ggccactttgaatgagagtg ttaccatcat 720 gatcatcctc acctcctacc tgctaattct caccaccatcctgaagatgg gctctgcaga 780 gggcaggcac aaagccttct ccacctgtgc ttcccacctcacagctatca ctgtcttcca 840 tggaacagtc ctttccattt attgcaggcc cagttcaggcaatagtggag atgctgacaa 900 agtggccacc gtgttctaca cagtcgtgat tcctatgctgaactctgtga tctacagcct 960 gagaaataaa gatgtgaaag aagctctcag aaaagtgatgggctccaaaa ttcactccta 1020 gggaagattt tattagcaca attcaggatt cccaagtagtggcaggcggg ggttcacggg 1080 agaggcacag tgttggagta c 1101 106 1351 DNAHomo sapiens misc_feature Incyte ID No 7478361CB1 106 caaaggccatatgattccca agccagtgat ttccactctg aataagagaa gggaaagagc 60 accagacacaacaaactgca gagcaaaata ggtaataaaa tgcatgattt agtattcagg 120 gaatcctgcgaaataatgtt gtagcttgtg ctcagtatag gaggcattgc acttccttct 180 gctgttcagacaggcaaaag gccatgggaa gtttcaacac cagttttgaa gatggcttca 240 ttttggtgggattctcagat tggccgcaac tggagcccat cctgtttgtc tttattttta 300 ttttctactccctaactctc tttggcaaca ccatcatcat cgctctctcc tggctagacc 360 ttcggctgcacacacctatg tacttctttc tctctcatct gtccctcctg gacctctgct 420 tcaccaccagcaccgtgccc cagctcctga tcaacctttg cggggtggac cgcaccatca 480 cccgtggagggtgtgtggct cagctcttca tctacctagc cctgggctcc acagagtgtg 540 tgctcctggtggtgatggcc tttgaccgct atgctgctgt ctgtcgtcca ctccactaca 600 tggccatcatgcacccccat ctctgccaga ccctggctat cgcctcctgg ggtgcgggtt 660 tcgtgaactctctgatccag acaggtctcg caatggccat gcctctctgt ggccatcgac 720 tgaatcacttcttctgtgag atgcctgtat ttctgaagtt ggcttgtgcg gacacagaag 780 gaacagaggccaagatgttt gtggcccgag tcatagtcgt ggctgttcct gcagcactta 840 ttctaggctcctatgtgcac attgctcatg cagtgctgag ggtgaagtca acggctgggc 900 gcagaaaggcttttgggact tgtgggtccc acctcctagt agttttcctt ttttatggct 960 cagccatctacacatatctc caatccatcc acaattattc tgagcgtgag ggaaaatttg 1020 ttgcccttttttatactata attaccccca ttctcaatcc tctcatttat acactaagaa 1080 acaaggacgtgaagggggct ctgtggaaag tactatggag gggcagggac tcagggtagg 1140 aggtgaaaaaatgagcagta aaattttctg taatagctct tcaatcacag atctttccct 1200 gttccttggagggcagttgg tcagtaggaa agccctcagt catcctcaga attggttttt 1260 gtttttgttttttggtggcg gggggaacag agtttcactc ttgttgccca ggctggagtg 1320 cagtggcacgatcttggctc actgcaacct t 1351 107 1301 DNA Homo sapiens misc_featureIncyte ID No 7482534CB1 107 ctttccataa cttagatgca aatcacagtc acttaattgacaagttttat ttctccagta 60 tgttcacttg attgacagca agccaaggca ttcttccatgtcctcagcct cctctttcct 120 tcctaggact ggcttccatg gaggtgaaga actgctgcatggtgacagag ttcatccttt 180 tgggaatccc acacacagag gggctggaga tgacactttttgtcttattc ttgcccttct 240 atgcctgcac tctactggga aatgtgtcta tccttgttgctgttatgtct tctgctcgcc 300 ttcacacacc tatgtatttc ttcctgggaa acttgtctgtgtttgacatg ggtttctcct 360 cagtgacttg tcccaaaatg ctgctctacc ttatggggctgagccgactc atctcctaca 420 aagactgtgt ctgccagctt ttcttcttcc atttcctcgggagcattgag tgcttcttgt 480 ttacggtgat ggcctatgac cgcttcactg ccatctgttatcctctgcga tacacagtca 540 tcatgaaccc aaggatctgt gtggccctgg ctgtgggcacatggctgtta gggtgcattc 600 attccagtat cttgacctcc ctcaccttca ccttgccatactgtggtccc aatgaagtgg 660 atcacttctt ctgtgacatt ccagcactgt tgcccttggcctgtgctgac acatccttag 720 cccagagggt gagcttcacc aacgttggcc tcatatctcttgtctgcttt ctgctaattc 780 ttttatccta cactagaatc acaatatcta tcttaagcattcgtacaact gagggccgtc 840 gccgtgcctt ctccacctgc agtgctcacc tcattgccatcctctgtgcc tatgggccca 900 tcatcactgt ctacctgcag cccacaccca accccatgctgggaaccgtg gtacaaattc 960 tcatgaatct ggtaggacca atgctgaacc ctttgatctataccttgagg aataaggaag 1020 taaaaacagc cctgaaaaca atattgcaca ggacaggccatgttcctgag agttagtaag 1080 agcagataaa tgggtgcatg gctctggaat tccttttgctttgacctaag aaatttcatt 1140 ctggaatctt catatgtgac aatgacttgg aattttcagcactgtgctga atgatatgga 1200 ccattatgct atatataata cattatcttt ttgcaatattttattttatt gtctaggttc 1260 tgcctcttca cctatcttca aagtcatata gtcttgttta t1301 108 1352 DNA Homo sapiens misc_feature Incyte ID No 7490493CB1 108actcgttctc tgctcaaaac ccataaggaa gggtattggc tccccccttt agacacgctt 60cacttttgga aagaaaagca gaggctttta aaggggaact tggcattaag agagagagag 120agagcaacct acaaacaaag atgtgccaga taacatttac tgttattttg tactgttaaa 180aacaagattt ctgaaccaaa tacttcactt ctttatttgt attttaaaga ttcactatta 240caagtcattg gccattcttc aaaagtgcca acctgaagtt ctgtcaaaat gagcttgtca 300ttacatctgc tgtcaagaat tccagacttg aactcacagc tatgggatta cgacttcata 360ctcgatatac caggtccata aaaacaatat aagtttcaac tactgaaatg aaaagacaaa 420atcaaagctg tgtggttgaa ttcatcctcc tgggcttttc taactttcct gagctccagg 480tgcagctctt tggggttttc ctagttattt atgtggtgac cctgatggga aatgccatca 540ttacagtcat catctcctta aaccagagcc tccacgttcc catgtacctg ttcctcctga 600acctatctgt ggtggaggtg agtttcagtg cagtcattac gcctgaaatg ctggtggtgc 660tctctactga gaaaactatg atttcttttg tgggctgttt tgcacagatg tatttcatcc 720ttctttttgg tgggactgaa tgttttctcc tgggagcgat ggcttatgac cgatttgctg 780caatttgcca tcctctgaac tacccagtga ttatgaacag aggggttttt atgaaattag 840taatattctc atgggcctta ggttttatgt taggtactgt tcaaacatca tgggtatcta 900gttttccctt ttgtggcctt aatgaaatta accatatatc ttgtgaaacc ccagcagtgt 960tagaacttgc atgtgcagac accttcttat ttgaaatcta tgccttcaca ggcaccattt 1020tgattgttat ggttcctttc ttgttgatcc tcttgtctta cattcgagtt ctgtttgcca 1080tcctgaagat gccatcaact actgggagac aaaaggcctt ttccacctgt gcctctcacc 1140tcacatctgt gaccctgttc tatggcacag ccaatatgac ttatttacaa cccaaatctg 1200gctactcacc cgaaaccaag aaactgatct cattggctta cacgttgctt acccctctgc 1260tcaatccgct catctatagc ttacgaaaca gtgagatgaa gaggactttg ataaaactat 1320ggcgaagaaa agtgatttta cacacattct ga 1352 109 1787 DNA Homo sapiensmisc_feature Incyte ID No 58001274CB1 109 atggaggtag aaggacttcagaatacagag gctaaatacc atgacagcag tgaacttaca 60 gaaggagcta ctgctcagcatgtgactttc tgggccacag acactattga gcatgttaca 120 caggcctttg tttccatggcaacaggacta caggaaggtt atggccagac tgacatagac 180 agtgttctag gtatcttcctgaggaaggat ctactagaaa ttatgttaca gcagaaagtt 240 ttcatggaga aatggaatcacacttcaaat gatttcattt tgttgggtct gcttccccca 300 aatcaaactg gaatatttctcttgtgcctt atcatcctca tattctttct ggcctcggtg 360 ggtaactcgg ccatgattcacctcatccac gtggatcctc gtctccacac accgatgtac 420 tttcttctca gccagctctcccttatggac ctgatgtaca tctccaccac cgtccccaag 480 atggcgtaca acttcctgtccggccagaaa ggcatctcct tcctgggatg tggtgtgcaa 540 agcttcttct tcctgaccatggcgtgttct gaaggcttac tcctgacctc catggcctac 600 gaccgttatt tggccatctgccactctctc tattatccta tccgcatgag taaaatgatg 660 tgtgtgaaga tgattggaggctcttggaca ctggggtcca tcaactcctt ggcacacaca 720 gtctttgccc ttcatattccctactgcagg tctagggcta ttgaccattt cttctgcgat 780 gtcccagcca tgttgcttcttgcctgtaca gatacttggg tctatgaata tatggttttt 840 gtaagtacaa gcctctttctccttttccct ttcattggca tcacttcttc ctgtggccga 900 gtcctatttg ctgtctatcatatgcactca aaggagggga gaaaaaaggc cttcaccacc 960 atttcaacac atttaactgtagtgatcttt tactatgcac cttttgtcta cacctatctt 1020 cggcccagga atctccgctcaccagctgaa gacaagatcc tggcagtctt ctacaccatc 1080 cttaccccca tgctcaatcccattatctac agcctgagga ataaggaagt cctgggggct 1140 atgaggagag tgtttgggatattctctttc ctgaaagaat aatcatggcc atccccactc 1200 cctttgtatt tcctctttccaagttgattc caacacgcta gagcagggtt gtccaataga 1260 aatacaacat aatttaaaattttctaatag gtacatttaa gcagtcaaat aaatttaaat 1320 aatatattta attcaaaacaatgttataat taatattaat attaacaata ttgatgttaa 1380 ttacatagca tactatttcaataaattata tgcaatatat tatagtacat gtttgtacat 1440 atattactat taacgtgataatgtttattc ttgtatattg acatagaatt tcttcatgta 1500 ataacaaaaa tttgttaatgttgcctttta ctctgtttgc attctaagtc ttcaaagtcc 1560 tgtgtttgtt ttatagagtgcagtgcagct tggacaaaac acatttcaag tgcccagtag 1620 tcagtgtcta tagtgttggacagcacattc ttagagcatc cccaatcaat agtttcagaa 1680 gttatatatg catgtgtatgtgcctgtatg gtgtatacaa acatattttg ttatatacca 1740 tattgctgat gaactgaaaattacagtaaa tgccatgcca aggtagg 1787 110 1251 DNA Homo sapiensmisc_feature Incyte ID No 7476809CB1 110 ctcatcttct gccagaatttctggggtgaa tgcagactgg aactcttagc taatggactg 60 tggctttatt ctgtatatactatgtccata aaatcaatgc acgacttcat tactgaaaat 120 ggaaagacaa aatcaaagctgtgtggttga attcatcctc ttgggctttt ctaactatcc 180 tgagctccag gggcagctctttgtggcttt cctggttatt tatctggtga ccctgatagg 240 aaatgccatt attatagtcatcgtctccct agaccagagc ctccacgttc ccatgtacct 300 gtttctcctg aacttatctgtggtggacct gagtttcagt gcagttatta tgcctgaaat 360 gctggtggtc ctctctactgaaaaaactac aatttctttt gggggctgtt ttgcacagat 420 gtatttcatc cttctttttggtggggctga atgttttctt ctgggagcaa tggcttatga 480 ccgatttgct gcaatttgccatcctctcaa ctaccaaatg attatgaata aaggagtttt 540 tatgaaatta attatattttcatgggcctt aggttttatg ttaggtactg ttcaaacatc 600 atgggtatct agttttcccttttgtggcct taatgaaatt aaccatatat cttgtgaaac 660 cccagcagtg ttagaacttgcatgtgcaga cacgtttttg tttgaaatct atgcattcac 720 aggcaccttt ttgattattttggttccttt cttgttgata ctcttgtctt acattcgagt 780 tctgtttgcc atcctgaagatgccatcaac cactgggaga caaaaggcct tttccacctg 840 tgccgctcac ctcacatctgtgaccctatt ctatggcaca gccagtatga cttatttaca 900 acccaaatct ggctactcaccggaaaccaa gaaagtgatg tcattgtctt actcacttct 960 gacaccactg ctgaatctgcttatctacag tttgcgaaat agtgagatga agagggcttt 1020 gatgaaatta tggcgaaggcgagtggtttt acacacaatc tgactgtgtt gagaagccat 1080 gtaagattta gtcactgcatgactgtattc aatctaaatt taataaattt agattcatta 1140 agtttgcatt ttttggcatgagtatgacta atttattgtg ttctccaagt ttgattgtat 1200 atcaggagca tctttatatgttaatgtttt tagttttttc accagtgcat a 1251 111 1401 DNA Homo sapiensmisc_feature Incyte ID No 7476048CB1 111 tttggttttg aatttgaatctgtattgaac tattttagcc tagatatact atttaacctt 60 cctgggtcca tttcctttctttaaaacaga agaaaaataa ctaccttaaa tttaaaattg 120 tatataaaat gactaataaaatgtatgcta tatatataaa gaatcttaat tatttttctt 180 tcctcatagt tcagtgtcttcaaccaacca tggcaatatt caataacacc acttcgtctt 240 cctcaaactt cctcctcactgcattccctg ggctggaatg tgctcatgtc tggatctcca 300 ttccagtctg ctgtctctacaccattgccc tcttgggaaa cagtatgatc tttcttgtca 360 tcattactaa gcggagactccacaaaccca tgtattattt cctctccatg ctggcagctg 420 ttgatctatg tctgaccattacgacccttc ccactgtgct tggtgttctc tggtttcatg 480 cccgggagat cagctttaaagcttgcttca ttcaaatgtt ctttgtgcat gctttctcct 540 tgctggagtc ctcggtgctggtagccatgg cctttgaccg cttcgtggct atctgtaacc 600 cactgaacta tgctactatcctcacagaca ggatggtcct ggtgataggg ctggtcatct 660 gcattagacc agcagttttcttacttcccc ttcttgtagc cataaacact gtgtcttttc 720 atgggggtca cgagctttcccatccatttt gctaccaccc agaagtgatc aaatacacat 780 attccaaacc ttggatcagcagtttttggg gactgtttct tcagctctac ctgaatggca 840 ctgacgtatt gtttattcttttctcctatg tcctgatcct ccgtactgtt ctgggcattg 900 tggcccgaaa gaagcaacaaaaagctctca gcacttgtgt ctgtcacatc tgtgcagtca 960 ctattttcta tgtgccactgatcagcctct ctttggcaca ccgcctcttc cactccaccc 1020 caagggtgct ctgtagcactttggccaata tttatctgct cttaccacct gtgctgaacc 1080 ctatcattta cagcttgaagaccaagacaa tccgccaggc tatgttccag ctgctccaat 1140 ccaagggttc atggggttttaatgtgaggg gtcttagggg aagatgggat tgaaggtagg 1200 aaattgtcag gacacgaattatgctttgga aagaaaggga cttggggcag tcttatccac 1260 aggtgttttg gttgctgagtcaattccaat tgaattttag gagtgggaag aagacagtaa 1320 ttttcccctg agcttatcaaagagttttat ttttaatttt taataccata atttaaacca 1380 aattaattga gcatatgtcc c1401 112 1162 DNA Homo sapiens misc_feature Incyte ID No 7476679CB1 112gtgctcttcc cacaggtggc cttttgcccc acccccagca tacaatgatg gaaatagcca 60atgtgagttc tccagaagtc tttgtcctcc tgggcttctc cacacgaccc tcactagaaa 120ctgtcctctt catagttgtc ttgagttttt acatggtatc gatcttgggc aatggcatca 180tcattctggt ctcccataca gatgtgcacc tccacacacc tatgtacttc tttcttgcca 240acctcccctt cctggacatg agcttcacca cgagcattgt cccacagctc ctggctaacc 300tctggggacc acagaaaacc ataagctatg gagggtgtgt ggtccagttc tatatctccc 360attggctggg ggcaaccgag tgtgtcctgc tggccaccat gtcctatgac cgctacgctg 420ccatctgcag gccactccat tacactgtca ttatgcatcc acagctttgc cttgggctag 480ctttggcctc ctggctgggg ggtctgacca ccagcatggt gggctccacg ctcaccatgc 540tcctaccgct gtgtgggaac aattgcatcg accacttctt ttgcgagatg cccctcatta 600tgcaactggc ttgtgtggat accagcctca atgagatgga gatgtacctg gccagctttg 660tctttgttgt cctgcctctg gggctcatcc tggtctctta cggccacatt gcccgggccg 720tgttgaagat caggtcagca gaagggcgga gaaaggcatt caacacctgt tcttcccacg 780tggctgtggt gtctctgttt tacgggagca tcatcttcat gtatctccag ccagccaaga 840gcacctccca tgagcagggc aagttcatag ctctgttcta caccgtagtc actcctgcgc 900tgaacccact tatttacacc ctgaggaaca cggaggtgaa gagcgccctc cggcacatgg 960tattagagaa ctgctgtggc tctgcaggca agctggcgca aatttagaga ctccagtgcc 1020ttctgagaag gaagatcaag tttacatcga gcaaagtgac cttggaagac agggcacttg 1080ggatgtcgtt tttcttctaa tattgtttga gctcaaggta gatggaaatc tgaaaggagt 1140gtgctcatgc catttccaga cc 1162 113 1197 DNA Homo sapiens misc_featureIncyte ID No 7486996CB1 113 aaataactga tattaactat gcctccaaac acagagcaggcattcaatga aagttacatc 60 atatctccaa taattacatt taattattgg agctctttcatgaatccatt ctttttatct 120 ttctaggact gtgtgattgg gttaaagggc tcagtgcggggactctgttt tctggtttca 180 gtaccacaat ggacacaggc aacaaaactc tgccccaggactttctctta ctgggctttc 240 ctggttctca aactcttcag ctctctctct ttatgctttttctggtgatg tacatcctca 300 cagttagtgg taatgtggct atcttgatgt tggtgagcacctcccatcag ttgcataccc 360 ccatgtactt ctttctgagc aacctctcct tcctggagatttggtatacc acagcagcag 420 tgcccaaagc actggccatc ctactgggga gaagtcagaccatatcattt acaagctgtc 480 ttttgcagat gtactttgtt ttctcattag gctgcacagagtacttcctc ctggcagcca 540 tggcttatga ccgctgtctt gccatctgct atcctttacactacggagcc atcatgagta 600 gcctgctctc agcgcagctg gccctgggct cctgggtgtgtggtttcgtg gccattgcag 660 tgcccacagc cctcatcagt ggcctgtcct tctgtggcccccgtgccatc aaccacttct 720 tctgtgacat tgcaccctgg attgccctgg cctgcaccaacacacaggca gtagagcttg 780 tggcctttgt gattgctgtt gtggttatcc tgagttcatgcctcatcacc tttgtctcct 840 atgtgtacat catcagcacc atcctcagga tcccctctgccagtggccgg agcaaagcct 900 tctccacgtg ctcctcgcat ctcaccgtgg tgctcatttggtatgggtcc acagttttcc 960 ttcacgtccg cacctctatc aaagatgcct tggatctgatcaaagctgtc cacgtcctga 1020 acactgtggt gactccagtt ttaaacccct tcatctatacgcttcgtaat aaggaagtaa 1080 gagagactct gctgaagaaa tggaagggaa aataaatctcctctaccaca acagatgtcc 1140 tgtaaatggt ctctgcatct atacagaggt tccaagtaagaatgtggagg aataggg 1197 114 1701 DNA Homo sapiens misc_feature Incyte IDNo 7490489CB1 114 ttctcccatt agctgtgaaa tttctgtctt aagtacatca caagatttttctgtcacgag 60 aacatggaaa gcaatcagac ctggatcaca gaagtcatcc tgttgggattccaggtggac 120 ccagctctgg agttgttcct ctttgggttt ttcttgctat tctacagcttaaccctgatg 180 ggaaatggga ttatcctggg gctcatctac ttggactcta gactgcacacacccatgtat 240 gtcttcctgt cacacctggc cattgtggac atgtcctatg cctcgagtactgtccctaag 300 atgctagcaa atcttgtgat gcacaaaaaa gtcatctcct ttgctccttgcatacttcag 360 acttttttgt atttggcgtt tgctattaca gagtgtctga ttttggtgatgatgtgctat 420 gatcggtatg tggcaatctg tcaccccttg caatacaccc tcattatgaactggagagtg 480 tgcactgtcc tggcctcaac ttgctggata tttagctttc tcttggctctggtccatatt 540 actcttattc tgaggctgcc tttttgtggc ccacaaaaga tcaaccactttttctgtcaa 600 atcatgtccg tattcaaatt ggcctgtgct gacactaggc tcaaccaggtggtcctattt 660 gcgggttctg cgttcatctt agtggggccg ctctgcctgg tgctggtctcctacttgcac 720 atcctggtgg ccatcttgag gatccagtct ggggagggcc gcagaaaggccttctctacc 780 tgctcctccc acctctgcgt ggtggggctt ttctttggca gcgccattgtcatgtacatg 840 gcccccaagt caagccattc tcaagaacgg aggaagatcc tttccctgttttacagcctt 900 ttcaacccga tcctgaaccc cctcatctac agccttagga atgcagaggtgaaaggggct 960 ctaaagagag tcctttggaa acagagatca atgtgaagaa tcatttgagatatcctgagt 1020 gtgtaagcat ggttctcatg accctgggtc ctgaaatttc ctttttaattctttaattta 1080 ccacacccaa tactgtttat ctttagactt cttataaaaa gagaaactggcctggcgtgg 1140 tggctgaagc ctgtaatccc aacactttgg gaggctgacc tgggcggattacctgaggtc 1200 aggagttcga gaccagccta accaacatgg cgaaacactg tctctattaaaaatacaaaa 1260 attagccggg cgtgctggtg ggcgcctgta atcccagctc tacttgggaggctgaggcag 1320 gagaatcgtt tgaacccagg aggcggaggt tgcactgagc cgagattgtaccactgcact 1380 ccagcctggg cgacagagca agactccctc tcaaaaataa ataaataaataaataaagag 1440 agagaaacta attactttta ctatttaagg cattgatacc aaacctgagataaacttatg 1500 aaacagaaaa tcacaatcta atcctactca tgaacataga tgcaaacctcttaaagaaaa 1560 tattaatgaa acaagtccat cagaatgaag taaggatgta ttataatgaaactatgtata 1620 cccttaaaat gcagcaataa tttaacatta aaacaaacaa caaaaataacttccccacat 1680 taacaaatta aagaatacat t 1701 115 939 DNA Homo sapiensmisc_feature Incyte ID No 7475304CB1 115 atggaacaac acaatctaacaacggtgaat gaattcattc ttacgggaat cacagatatc 60 gctgagctgc aggcaccattatttgcattg ttcctcatga tctatgtgat ctcagtgatg 120 ggcaatttgg gcatgattgtcctcaccaag ttggactcca ggttgcaaac ccctatgtac 180 ttttttctca gacatctggctttcatggat cttggttatt caacaactgt gggacccaaa 240 atgttagtaa attttgttgtggataagaat ataatttctt attatttttg tgcaacacag 300 ctagctttct ttcttgtgttcattggtagt gaacttttta ttctctcagc catgtcctac 360 gacctctatg tggccatctgtaaccctctg ctatacacag taatcatgtc acgaagggta 420 tgtcaggtgc tggtagcaatcccttacctc tattgcacat tcatttctct tctagtcacc 480 ataaagattt ttactttatccttctgtggc tacaacgtca ttagtcattt ctactgtgac 540 agtctccctt tgttacctttgctttgttca aatacacatg aaattgaatt gataattctg 600 atctttgcag ctattgatttgatttcatct cttctgatag ttcttttatc ttacctgctc 660 atccttgtag ccattctcaggatgaattct gctggcagac aaaaggcttt ttctacctgt 720 ggagcccacc tgacagtggtcatagtgttc tatgggactt tgcttttcat gtacgtgcag 780 cccaagtcca gtcattcctttgacactgat aaagtggctt ccatatttta caccctggtt 840 atccccatgt tgaatcccttgatctatagt ttacgaaaca aagatgtaaa atatgcccta 900 cgaaggacat ggaataacttatgtaatatt tttgtttaa 939 116 973 DNA Homo sapiens misc_feature Incyte IDNo 7475248CB1 116 tttctcataa atgaccagaa aaaattatac ctcactgact gagttcgtcctattgggatt 60 agcagacacg ctggagctac agattatcct ctttttgttt tttcttgtgatttatacact 120 tacagtactg ggaaatctcg ggatgatcct cttaatcagg atcgattcccagcttcacac 180 acccatgtat ttcttcctgg ctaacctgtc ctttgtggac gtttgtaactcaactaccat 240 caccccaaag atgctggcag atttattatc agagaagaaa accatctcttttgctggctg 300 cttcctacag atgtacttct ttatctccct ggcgacaacc gaatgcatcctctttgggtt 360 aatggcctat gacaggtatg cggccatatg tcgcccgctg ctttactccttgatcatgtc 420 caggaccgtc tacctaaaaa tggcagccgg ggcttttgct gcagggttgctgaacttcat 480 ggtcaacaca agccatgtca gcagcttgtc attctgtgac tccaatgtcatccatcactt 540 cttctgtgac agtcccccac ttttcaagct ctcttgttct gacacaatcctgaaagaaag 600 cataagttct attttggctg gtgtgaatat tgtggggact ctgcttgtcatcctctcctc 660 ctactcctac gttctcttct ccattttttc tatgcattcg ggggaggggaggcacagagc 720 tttctccacg tgtgcctctc acctgacagc cataattctg ttctatgccacctgcatcta 780 tacttacctg agacctagtt ccagctactc cctgaatcag gacaaagtggcttctgtgtt 840 ctacacagtg gtgattccca tgttgaatcc tctgatctac agcctcaggagtaaggaagt 900 aaagaaggct ttagcgaatg taattagcag gaaaaggacc tcttcctttctgtgattgtt 960 tggctaaaaa tct 973 117 1204 DNA Homo sapiens misc_featureIncyte ID No 7475191CB1 117 gaaatgtcct taatcttttt aggataagcg gttgttctctctcttttgct ctctagattt 60 cacaaggaac aagggcttag aactaaatgt tgatgaattactctagtgcc actgaatttt 120 atctccttgg cttccctggc tctgaagaac tacatcatatcctttttgct atattcttct 180 ttttctactt ggtgacatta atgggaaaca cagtcatcatcatgattgtc tgtgtggata 240 aacgtctgca gtcccccatg tatttcttcc tcggccacctctctgccctg gagatcctgg 300 tcacaaccat aatcgtcccc gtgatgcttt ggggattgctgctccctggg atgcagacaa 360 tatatttgtc tgcctgtgtt gtccagctct tcttgtaccttgctgtgggg acaacagagt 420 tcgcattact tggagcaatg gctgtggacc gttatgtggctgtctgtaac cctctgaggt 480 acaacatcat tatgaacaga cacacctgca actttgtggttcttgtgtca tgggtgtttg 540 ggtttctttt tcaaatctgg ccggtctatg tcatgtttcagcttacttac tgcaaatcaa 600 atgtggtgaa caattttttt tgtgaccgag ggcaattgctcaaactatcc tgcaataata 660 ctcttttcac ggagtttatc ctcttcttaa tggctgtttttgttctcttt ggttctttga 720 tccctacaat tgtctccaac gcctacatca tctccaccattctcaagatc ccgtcatcct 780 ctggccggag gaaatccttc tccacttgtg cctcccacttcacctgtgtt gtgattggct 840 acggcagctg cttgtttctc tacgtgaaac ccaagcaaacgcaggcagct gattacaatt 900 gggtagtttc cctgatggtt tcagtagtaa ctcctttcctcaatcctttc atcttcaccc 960 tccggaatga taaagtcata gaggcccttc gggatggggtgaaacgctgc tgtcaactat 1020 tcaggaatta gccttgctct gaggactttt acatggtaaagcacttagta tggattctag 1080 aataatctga aaagaacttg ctcatctttg aactgcatcataattattgc cattatcaaa 1140 tgatttgcat gcaacaaaat acttttaagt tacagctacggtttttagta tgcttagttg 1200 ttac 1204 118 2011 DNA Homo sapiensmisc_feature Incyte ID No 7480413CB1 118 ggggataaat atggcattttgaaaataaat attttgttta tatttcaaat aaatacttga 60 tatttagggc atctgcagcatttattgctg tgatttcttg taaaaatatt tctctgcctg 120 acagttaata aattaaatgccttagatttc actggggact gggaagaggg ctcactgtgc 180 ctactgctgc tctcctgctcggcactcgtt ctgcactcca agctactctc ctcaggcagg 240 cgggactctc cctctgctcctctgccccag tcagcactac ttatggaatg caaccttgtg 300 aggaatagca gaataaattgaaaagttttc atgaggaaag tggacttaaa tggagatata 360 taatggtaga agaaatttaaggagatttcc agttttcaga ttatttcatg gtattagtta 420 tgatatttgt accattaacaatattaatat taaccttatc agccatgatt tccatcactg 480 agtcctggat gagctactgtatccaaaaag tagtgaaaat ctcaacccaa cactaacact 540 gtgttacaga cctaacgtgcattccctact tcagtctcta accatcccac aaggccagta 600 tacttgtgtt cttaattctggggggaaata agacatagag tgtacctgtc ttcactcttg 660 acttagctca ggaatagtcacctccccaga tctgtttcgt agttcacttt agcttgtggc 720 caacatgcga cttgacctaagatttgaact tatgatttta tgtcagttta actcaatatt 780 tagaaaaata attcaaagcacatgtcttac cagaaaaagg ttaggaaagc catgtacata 840 ggaaagattt aaaattaatgactttttttt cctcaggggg aaactgtgag ccagtcatgt 900 gctcagggaa tcagacttctcagaatcaaa cagcaagcac tgatttcacc ctcacgggac 960 tctttgctga gagcaagcatgctgccctcc tctacaccgt gaccttcctt cttttcttga 1020 tggccctcac tgggaatgccctcctcatcc tcctcatcca ctcagagccc cgcctccaca 1080 cccccatgta cttcttcatcagccagctcg cgctcatgga tctcatgtac ctatgcgtga 1140 ctgtgcccaa gatgcttgtgggccaggtca ctggagatga taccatttcc ccgtcaggct 1200 gtgggatcca gatgttcttccacctgaccc tggctggagc tgaggttttc ctcctggctg 1260 ccatggccta tgaccgatatgctgctgttt gcagacctct ccattaccca ctgctgatga 1320 accagagggt gtgccagctcctggtgtcag cctgctgggt tttgggaatg gttgatggtt 1380 tgttgctcac ccccattaccatgagcttcc ccttttgcca gtctaggaaa atcctgagtt 1440 ttttctgtga gactcctgccctgctgaagc tctcctgctc tgacgtctcc ctctataaga 1500 tgctcacgta cctgtgctgcatcctcatgc ttctcacccc catcatggtc atctccagct 1560 catacaccct catcctgcatctcatccaca ggatgaattc tgccgccggc cgcaggaagg 1620 ccttggccac ctgctcctcccacatgatca tagtgctgct gctcttcggt gcttccttct 1680 acacctacat gctccggagttcctaccaca cagctgagca ggacatgatg gtgtctgcct 1740 tttacaccat cttcactcctgtgctgaacc ccctcattta cagtctccgc aacaaagatg 1800 tcaccagggc tctgaggagcatgatgcagt caagaatgaa ccaagaaaag tagtaaagga 1860 caagcattgt cccctcctctttctataatt ccgttactcc ctatctctcc tctcttttgc 1920 cctcaggtct ccgggtccccagcacaaagc ccactcatat tttccttctt tcttatacgt 1980 ggcgttttcc ctccatactgcttattgctc c 2011 119 1402 DNA Homo sapiens misc_feature Incyte ID No7476165CB1 119 tggttttttc ctgttaaccc aaggtattta caataagaaa gaagaaccatatgaaagaag 60 aatttccaga ccacaaagag aagactggcc cagtttttct gtgtagtcatgatgacctgg 120 atgcttgaga gcagtatgtg atcaatgatt ttgccacctc atgtcaccataatccaagtt 180 ctaacatatc ttcatcaaag gtaggacctg gaagagagtc atccccatcatggaccagat 240 caaccacact aatgtgaagg agtttttctt cctggaactt acacgttcccgagagctgga 300 gtttttcttg tttgtggtct tctttgctgt gtatgtagca acagtcctgggaaatgcact 360 cattgtggtc actattacct gtgagtcccg cctacacact cctatgtactttctcctgcg 420 gaacaaatca gtcctggaca tcgttttttc atctatcacc gtccccaagttcctggtgga 480 tcttttatca gacaggaaaa ccatctccta caatgactgc atggcacagatctttttctt 540 ccactttgct ggtggggcag atattttttt cctctctgtg atggcctatgacagatacct 600 tgcaatcgcc aagcccctgc actatgtgac catgatgagg aaagaggtgtgggtggcctt 660 ggtggtggct tcttgggtga gtggtggttt gcattcaatc atccaggtaattctgatgct 720 tccattcccc ttctgtggcc ccaacacact ggatgccttc tactgttatgtgctccaggt 780 ggtaaaactg gcctgcactg acacctttgc tttggagctt ttcatgatctctaacaacgg 840 actggtgacc ctgctctggt tcctcctgct cctgggctcc tacactgtcattctggtgat 900 gctgagatcc cactctgggg aggggcggaa caaggccctc tccacgtgcacgtcccacat 960 gctggtggtg actcttcact tcgtgccttg tgtttacatc tactgccggcccttcatgac 1020 gctgcccatg gacacaacca tatccattaa taacacggtc attacccccatgctgaaccc 1080 catcatctat tccctgagaa atcaagagat gaagtcagcc atgcagaggctgcagaggag 1140 acttgggcct tccgagagca gaaaatgggg gtgagcagtc agatggagagtggaagtctg 1200 tctgacttag ttttctcaaa atgctagcct aagagtaaca ggtcgctagctcttcttcca 1260 ctacttcatt gtatatcttc atagccgctc gattctatta gcgggagtatacaaacaaaa 1320 agaagaaatg agattaaaca atgtgagcta tcgagcttgt ggactcaggagaagaagagg 1380 gtataaggtt gaaatcaata cc 1402 120 2201 DNA Homo sapiensmisc_feature Incyte ID No 7478345CB1 120 agtttctttt gtgcctcagcatccatctag agagtacaaa ggggcctagg tcatagcagc 60 tgcttcaccc ctcactctggagagagatcc aaagatcaga gctagagtct ttacatatga 120 gagtcaggcc ccagacacaggacgagagcc caggaaacag tgagaaaggc gtcgaatttg 180 gagtcaagag acctggattcaagttccagg cctgccactt tctagatatt acctcagaca 240 cattatttaa tctctctgagacccatggct cattcagaga aaggtattaa ttctctcact 300 tgattttgag aggaactgtgtggcaagtgc tttaccaaat tacagaaatg ttgcttgtta 360 tttctaaata acttctcttcttggctgtgc ctcagcttct ggcctggagt gatggctggg 420 gaaaaccata ctacactgcctgaattcctc cttctgggat tctctgacct caaggccctg 480 cagggccccc tgttctgggtggtgcttctg gtctacctgg tcaccttgct gggtaactcc 540 ctgatcatcc tcctcacacaggtcagccct gccctgcact cccccatgta cttcttcctg 600 cgccaactct cagtggtggagctcttctac accactgaca tcgtgcccag gaccctggcc 660 aatctgggct ccccgcatccccaggccatc tctttccagg gctgtgcagc ccagatgtac 720 gtcttcattg tcctgggcatctcggagtgc tgcctgctca cggccatggc ctatgaccga 780 tatgttgcca tctgccagcccctacgctat tccaccctct tgagcccacg ggcctgcatg 840 gccatggtgg gtacctcctggctcacaggc atcatcacgg ccaccaccca tgcctccctc 900 atcttctctc taccttttcgcagccacccg atcatcccgc actttctctg tgacatcctg 960 ccagtactga ggctggcaagtgctgggaag cacaggagcg agatctccgt gatgacagcc 1020 accatagtct tcattatgatccccttctct ctgattgtca cctcttacat ccgcatcctg 1080 ggtgccatcc tagcaatggcctccacccag agccgccgca aggtcttctc cacctgctcc 1140 tcccatctgc tcgtggtctctctcttcttt ggaacagcca gcatcaccta catccggccg 1200 caggcaggct cctctgttaccacagaccgc gtcctcagtc tcttctacac agtcatcaca 1260 cccatgctca accccatcatctacaccctt cggaacaagg acgtgaggag ggccctgcga 1320 cacttggtga agaggcagcgcccctcaccc tgaagggact cggatgtctg ctcactcact 1380 cagtgctcat cctcccactcttcagggact ggatttaaac cccactctca cagaaatcat 1440 gcagcacctc aaaggaaaaggcttcctgga agaaagtgct gaaattaaaa cagagataaa 1500 tctacatatt gcctcttatcccagagtcca cactcactat cagagcatgg gttattaggt 1560 caaggtagaa tgaaagtgattgctgcccta gggaaaggac atttatttag catcttctag 1620 attgttctgg atccctgagcacagtgattg ccatggctgc accggtagcc agaggtccat 1680 gtcagtcatg aaagcaggtgtctgtgaact tgacatccaa ctaagtggcc cacccaaagc 1740 ctgtggagga gtttacctagcccctctgtt acattttctt ccaccacctg tgtctgagct 1800 ttcctctact cagtggaacatctgttctcc ccttggcctt caggaagagg ggcatctgag 1860 ggttccagtc ataaggctctctccttccca agataccagc acaaaaggga agatggtcag 1920 atggtatcaa aaaggaccaagttaaacatc aggaaaagtt atctcccagg acagcctata 1980 catgtctccc agaaacacactggggtgtcc tactgtgggt gcttttggga aagagctggt 2040 cagggattcc agaagacccaccagcttgag aggcaggatc cagagctgga gctaaccagg 2100 gagccagaag caagacaaggtggaaggaaa acactcccat ccctctgtgc tgaggtgcca 2160 ccggctgccc acttccctcagcccagggac agatgtttct c 2201 121 1193 DNA Homo sapiens misc_featureIncyte ID No 7475245CB1 121 ttgaactttt tcagatttcc caaaatttct gttctttgctgataaaaatt agctatccta 60 cttcttctga tatcttttta caggatacac ccaaaactaaaatttagact atataatgga 120 gaataagttt taggtttttt tctcctctaa tcctgcataaattggagaca tgggcaagga 180 aaactgcacc actgtggctg agttcattct ccttggactatcagatgtcc ctgagttgag 240 agtctgcctc ttcctgctgt tccttctcat ctatggagtcacgttgttag ccaatctggg 300 catgactgca ctgattcagg tcagctctcg gctccacacccccgtgtact ttttcctcag 360 ccacttgtcc tttgtagatt tctgctactc ctcaataattgtgccaaaga tgttggctaa 420 tatctttaac aaggacaaag ccatctcctt cctagggtgcatggtgcaat tctacttgtt 480 ttgcacatgt ggagtcactg aggtcttcct gctggccgtgatggcctatg accgctttgt 540 ggccatctgt aaccccctgc tgtacatggt gaccatgtctcagaagctgc gtgtggagct 600 gacctcttgc tgctacttct gtgggacggt gtgttctctgattcactcgt ccttagctct 660 taggatcctc ttctatagat ctaatgtgat taaccacttcttctgtgatc taccccctct 720 cctaagtctt gcttgctctg atgtcactgt gaatgagacactgctgttcc tggtggccac 780 tttgaatgag agtgttacca tcatgatcat cctcacctcctacctgctaa ttctcaccac 840 tatcctgaag atacactctg cagagagcag gcacaaagctttctccacct gtgcctccca 900 cctcacagcc atcactgtct cccatggaac aatcctttacatttattgca ggccgagttc 960 aggcaacagt ggagatgttg acaaagtggc caccgtgttctacacagttg tgattcccat 1020 gctgaacccc ctgatctaca gcctgagaaa taaggatgtgaacaaagctc tcagaaaagt 1080 gatgggctcc aaaattcact cctagggaag attttattcacagaattcag gatccccaag 1140 ttgtggcaag tgaaggttcg taggaggggt gcagtgttggagtagagaga aga 1193 122 1036 DNA Homo sapiens misc_feature Incyte ID No7485481CB1 122 ccttttgaaa caatttctcc ataggcaaca cagacttggc ctatactaaggcaatgccta 60 atttcacgga tgtgacagaa tttactctcc tggggctgac ctgtcgtcaggagctacagg 120 ttctcttttt tgtggtgttc ctagcggttt acatgatcac tctgttgggaaatattggta 180 tgatcatttt gattagcatc agtcctcagc ttcagagtcc catgtactttttcctgagtc 240 atctgtcttt tgcggacgtg tgcttctcct ccaacgttac ccccaaaatgctggaaaact 300 tattatcaga gacaaaaacc atttcctatg tgggatgctt ggtgcagtgctactttttca 360 ttgccgttgt ccacgtggag gtctatatcc tggctgtgat ggcctttgacaggtacatgg 420 ccggctgcaa ccctctgctt tatggcagta aaatgtctag gactgtgtgtgttcggctca 480 tctctgtgcc ttatgtctat ggattctctg tcagcctaat atgcacactatggacttatg 540 gcttatactt ctgtggaaac tttgaaatca atcacttcta ttgtgcagatccccctctca 600 tccagattgc ctgtgggaga gtgcacatca aagaaatcac aatgattgttattgctggaa 660 ttaacttcac atattccctc tcggtggtcc tcatctccta cactctcattgtagtagctg 720 tgctacgcat gcgctctgcc gatggcagga ggaaggcgtt ctccacctgtgggtcccact 780 tgacggctgt ttctatgttt tatgggaccc ccatcttcat gtatctcaggagacccactg 840 aggaatccgt agagcagggc aaaatggtgg ctgtgtttta caccacagtaattcctatgt 900 tgaatcccat gatctacagt ctgagaaata aggatgtaaa agaagcagtcaacaaagcaa 960 tcaccaagac atatgtgagg cagtaaaact gtagtggata ttgttgtccctattataaat 1020 agggtcctgt tataaa 1036 123 1096 DNA Homo sapiensmisc_feature Incyte ID No 7482835CB1 123 aaatctaaaa ctaagagctcctgtctcctg gataccccag atccctgaat atgttaaccc 60 ctaataatgc ctgctccgtgcctacctctt tccggctcac tggcatccct ggcctggaat 120 ccctgcacat ctggctctccatcccctttg gctccatgta cctggtagct gtgctgggga 180 acataaccat cctggcagtggtaaggatgg agtacagcct gcatcagccc atgtacttct 240 tcctgtgcat gttggctgtcattgacttgg tcctgtcaac ctctaccatg cccaaactac 300 tggccatctt ctggtttggtgcccacaaca ttggtgttaa tgcctgtttg gcccagatgt 360 tcttcattca ttgctttgccactgttgagt caggcatctt ccttgccatg gcttttgatc 420 actatgtggc catctgtgacccactgcatc ataccttgtt gctcacccat gctgtggtgg 480 gtcgtttggg gctggctgccctcctccggg gggtaatcta cattggacct ctgcccctag 540 tgatttgtct gaggttgcccctttaccaca cccaaatcat tgcccattcg tactgtgagc 600 acatggctgt ggtcaccttggcatgtggtg tgacaacaag ggtcaacaac ttatatggaa 660 tggggattgg ctttctggtattaatcctgg attcattggc catcactgcc tcctatgtga 720 tgattttcag ggctgtaatgggcttggcca cctctgaagc caggcttaaa accttaggga 780 catgtggctc tcacatctgtgccatcctcg tcttctacat ccccattgct gtttcctctc 840 tcacacaccg ctttggccatcgtgtgcctc cccatatcca tatccatatc catatccata 900 tccatatcca tatccatatccatatccttt tggccaacat ttacctcctc atcccaccta 960 tcctcaaccc aatagtctatgctgtccaca caaagcagat ccgagaggct cttctccata 1020 ttaaggcaag gactcaaaccaggtgactgt tctatatctt tttattttag attcaggggt 1080 acatgtaaag gtttgt 1096124 1133 DNA Homo sapiens misc_feature Incyte ID No 7475100CB1 124tcatgatttt gccaacatca atgctttttg tcctaaatca aagtttctcc ttactctcct 60ctttcagtta gcatgagagt tgtcacagcc gacagaggca atggatgaag ccaatcactc 120tgtggtctct gagtttgtgt tcctgggact ctctgactcg cggaagatcc agctcctcct 180cttcctcttt ttctcagtgt tctatgtgtc aagcctgatg ggaaatctcc tcattgtgct 240aactgtgacc tctgaccctc gtttacagtc ccccatgtac ttcctgctgg ccaacctttc 300catcatcaat ttggtatttt gttcctccac agctcccaag atgatttatg accttttcag 360gaagcacaag accatctctt ttgggggctg tgtagttcag atcttcttta tccatgcagt 420tgggggaact gagatggtgc tgctcatagc catggctttt gaccgatatg tggccatatg 480taagcctctc cactacctga ccatcatgaa cccacaaagg tgcattttgt ttttagtcat 540ttcctggatt ataggtatta ttcactcagt gattcagttg gcttttgttg tagacctgct 600gttctgtggc cctaatgaat tagatagttt cttttgtgat cttcctcgat ttatcaaact 660ggcttgcata gagacctaca cattgggatt catggttact gccaatagtg gatttatttc 720tctggcttct tttttaattc tcataatctc ttacatcttt attttggtga ctgttcagaa 780aaaatcttca ggtggtatat tcaaggcttt ctctatgctg tcagctcatg tcattgtggt 840ggttttggtc tttgggccat taatcttttt ctatattttt ccatttccca catcacatct 900tgataaattc cttgccatct ttgatgcagt tatcactccc gttttgaatc cagtcatcta 960tacttttaga aataaagaga tgatggtggc aatgagaaga cgatgctctc agtttgtgaa 1020ttacagtaaa atcttttaaa tatattgaga atatacaaaa aggcaaatta tactagaatt 1080tcagacagat atgtgttaag taagctatgt taaatttaac cagaatatca ctt 1133 125 1198DNA Homo sapiens misc_feature Incyte ID No 7475185CB1 125 attacacataaatacataaa caatgaaacc ctaaggtaaa aaaaaaaaag tctgaacttt 60 ccttgaatgatacatctgtt catattaacc ttcatgtata tattaatgaa gatgaagcca 120 tcaaatttataacattttaa tgtgctgttc tcattagggt tcatttagtc agcagctact 180 tcgtctcatgaattccctga aggacgggaa tcacaccgct ctgacggggt tcatcctatt 240 gggcttaacagatgatccaa tccttcgagt catcctcttc atgatcatcc tatctggtaa 300 tctcagcataattattctta tcagaatttc ttctcagctc catcatccta tgtatttctt 360 tctgagccacttggcttttg ctgacatggc ctattcatct tctgtcacac ccaacatgct 420 tgtaaacttcctggtggaga gaaatacagt ctcctacctt ggatgtgcca tccagcttgg 480 ttcagcggctttctttgcaa cagtcgaatg cgtccttctg gctgccatgg cctatgaccg 540 ctttgtggcaatttgcagtc cactgcttta ttcaaccaaa atgtccacac aagtcagtgt 600 ccagctactcttagtagttt acatagctgg ttttctcatt gctgtctcct atactacttc 660 cttctattttttactcttct gtggaccaaa tcaagtcaat cattttttct gtgatttcgc 720 tcccttacttgaactctcct gttctgatat cagtgtctcc acagttgttc tctcattttc 780 ttctggatccatcattgtgg tcactgtgtg tgtcatagcc gtctgctaca tctatatcct 840 catcaccatcctgaagatgc gctccactga ggggcaccac aaggccttct ccacctgcac 900 ttcccacctcactgtggtta ccctgttcta tgggaccatt accttcattt atgtgatgcc 960 caattttagctactcaactg accagaacaa ggtggtgtct gtgttgtaca cagtggtgat 1020 tcccatgttgaaccccctga tctacagcct caggaacaag gagattaagg gggctctgaa 1080 gagagagcttgttagaaaaa tactttctca tgatgcttgt tattttagta gaacttcaaa 1140 taatgatattacatagaacc ctatctcttc tcttgagaat actcaatgca cgtgtaga 1198 126 1397 DNAHomo sapiens misc_feature Incyte ID No 7477369CB1 126 atttccattcaaaacaatat accaaatgag aaggatggaa agaatagtca aggtaagttt 60 tatgagaagataaaatttct gaaagtagat aattggaaat gaatcttttg cttctattga 120 atctgactttcctttttttt tttttttttt ttcgtgatac aggcttctgc ctatgaatca 180 agacaatggatgtgggcaat aagtctacca tgtctgaatt tgttttgctg gggctctcta 240 attcctgggaactacagatg tttttcttta tggtgttttc attgctttat gtggcaacaa 300 tggtgggtaacagcctcata gtcatcacag ttatagtgga ccctcaccta cactctccta 360 tgtatttcctgcttaccaat ctttcaatca ttgatatgtc tcttgcttct ttcgccaccc 420 caaagatgattacagattac ctaacaggtc acaaaaccat ctcttttgat ggctgcctta 480 cccagatattctttctccac cttttcactg gaactgagat catcttactc atggccatgt 540 cctttgataggtatattgca atatgcaagc ccctgcacta tgcttctgtc attagtcccc 600 aggtgtgtgttgctctcgtg gtggcttcct ggattatggg agttatgcat tcaatgagtc 660 aggtcatatttgccctcacg ttaccattct gtggtcccta tgaggtagac agctttttct 720 gtgaccttcctgtggtgttc cagttggctt gtgtggatac ttatgttctg ggcctcttta 780 tgatctcaacaagtggcata attgcgttgt cctgttttat tgttttattt aattcatatg 840 ttattgtcctggttactgtg aagcatcatt cttccagagg atcatctaag gccctttcta 900 cttgtacagctcatttcatt gttgtcttct tgttctttgg gccatgcatc ttcatctaca 960 tgtggccactaagcagcttt ctcacagaca agattctgtc tgtgttttat accatcttta 1020 ctcccactctgaacccaata atctatactt tgaggaatca agaagtaaag atagccatga 1080 ggaaactgaaaaataggttt ctaaatttta ataaggcaat gccttcatag tttttgtgac 1140 acagaacattagacacaatg ctgtgttagg cttttctttc tagagggttc ttaccaaatt 1200 gtaattgccaagaatttgtg agggctcaag ttcagtgcat tttgaaacta ttctcatgaa 1260 tgtgaatgtgttcaaaatac atttgaaatt tcagaaaagc aagttaaaag aaataaagac 1320 tataaaaatgtcaggagtga cagttccagt taggacattc aatatcaata atcaatttat 1380 tggaaaagaggaccaag 1397 127 1051 DNA Homo sapiens misc_feature Incyte ID No7495138CB1 127 ttcgttacag gccctgtttc cctgagctct cacctctgat acaagccttaaagaagagta 60 aatgagacag aataacaata ttacagaatt tgtcctcctg ggcttttctcaggatcctgg 120 tgtgcaaaaa gcattatttg tcatgttttt actcacatac ttggtgacagtggtggggaa 180 cctgctcatt gtggtggata ttattgccag cccttccttg ggttccccaatgtatttctt 240 ccttgcctgc ctgtcattta tagatgctgc atattccact accatttctcccaagttaat 300 tgtaggctta ttctgtgata aaaagactat ttccttccaa ggttgcatgggccagctatt 360 tatagaccat ttctttggtg gggctgaggt cttccttctg gtggtgatggcctgtgatcg 420 ctatgtggcc atctgtaagc cactgcacta tttgaccatc atgaatcgacaggtttgctt 480 ccttctgttg gtggtggcca tgattggagg ttttgtacat tctgcgtttcaaattgttgt 540 gtacagtctc cctttctgtg gtcccaatgt cattgttcat ttcagttgtgacatgcaccc 600 attactggaa ctggcatgca ctgacaccta ctttataggc ctcactgttgttgtcaatag 660 tggagcaatc tgtatggtca ttttcaacct tctgttaatc tcctatggagtcatcctaag 720 ctcccttaaa acttacagtc aggaaaagag gggtaaagcc ttgtctacctgcagctccgg 780 cagtaccgtt gttgtcctct tttttgtacc ctgtattttc atatatgttagacctgtttc 840 aaactttcct actgataagt tcatgactgt gttttatacc attatcacacacatgctgag 900 tcctttaata tatacgttga gaaattcaga gatgagaaat gctatagaaaaactcttggg 960 taaaaagtta actatattta ttataggagg agtgtccgtc ctcatgtaggtaaggaggta 1020 tgtagtcaag gtcttcccag tgaagttttc a 1051 128 1236 DNAHomo sapiens misc_feature Incyte ID No 7475830CB1 128 agtaaaagactcccctccct caggcaagat tggcctctgt cattagagag gtaagatgta 60 tgtttttgcccacatgatga tatgattcaa ggcaagaaga caacaatcat cacctttacc 120 caacactgacagggaacatg agaagtatct tttttatttt tcaactgcga caaaatctac 180 aaaacctgttaggataaatg gctgaagtta atatcattta tgtcactgta ttcattctga 240 aaggaattaccaaccggcca gagcttcagg ccccgtgctt tggggtgttt ttagttatct 300 atctggtcacagtgctgggc aatcttgggt tgattacttt aatcaagatt gatactcgac 360 tccacacacctatgtactat ttcctcagcc acctggcctt tgttgacctt tgttactcct 420 ctgctattacaccgaagatg atggtgaatt ttgttgtgga acgcaacacc attcctttcc 480 atgcttgtgcaacccaactg ggttgttttc tcaccttcat gatcactgag tgtttccttc 540 tagcctccatggcctacgat tgctatgtcg ccatctgtag tcccctgcat tattcaacac 600 tgatgtcaagaagagtctgc attcaactgg tggcagttcc atatatatac agcttcctgg 660 ttgccctcttccacaccgtt atcactttcc gtctgactta ctgtggccca aacttaatta 720 accatttctattgtgatgac ctccccttct tagctctgtc ctgctcagac acacacatga 780 aggaaattctgatatttgcc tttgctggct ttgatatgat ctcttcctct tccattgtcc 840 tcacctcctacatctttatt attgccgcta tcctaaggat ccgctctact caggggcaac 900 acaaagccatttccacctgt ggctcccata tggtgactgt cactattttc tatggcacac 960 tgatctttatgtacctacag cccaaatcaa atcactcctt ggacacagac aagatggctt 1020 ctgtattttacacagtggtg atccccatgt taaaccccct aatctatagt ctaaggaaca 1080 aagaagtgaaagatgcctca aagaaagcct tggataaagg ttgtgaaaac ttacagatat 1140 taacatttttaaaaataaga aaactttatt aaacaagcag gaaataaatc aaactttttc 1200 ttgtaattatttcccaatga actgaaaatg tagctg 1236 129 1287 DNA Homo sapiens misc_featureIncyte ID No 7476161CB1 129 tctacatatt catgacagta atgcaaactg agctcattttctttccccat aggtgagatt 60 ccttacagcc atgcagagga gcaatcatac agtgactgagtttatactgc tgggcttcac 120 cacagaccca ggaatgcagc tgggcctctt cgtggtgttcctgggcgtgt actctctcac 180 tgtggtagga aatagcaccc tcatcgtgtt gatctgtaatgactcctgcc tccacacacc 240 catgtatttt ttcactggaa atctgtcgtt tctggatctctggtattctt ctgtctacac 300 cccaaagatc ctagtgacct gcatctctga agacaaaagcatctcctttg ctggctgcct 360 gtgtcagttc ttcttctctg cagggctggc ctatagtgagtgctacctgc tggctgccgt 420 ggcttatgac cgctacgtgg ccatctccaa gcccctgctttatgcccagg ccatgtccat 480 aaagctgtgt gcattgctgg tagcagtctc atattgtggtggctttatta actcttcaat 540 catcaccaag aaaacgtttt cctttaactt ctgccgtgaaaacatcattg atgacttttt 600 ctgtgatttg cttcccttgg tggagctggc ctgtggcgagaagggcggct ataaaattat 660 gatgtacttc ctgctggcct ccaatgtcat ctgccccgcagtgctcatcc tggcctccta 720 cctctttatc atcaccagtg tcttgaggat ctcctcctccaagggctacc tcaaagcctt 780 ctccacatgc tcctcccacc tgacctctgt cactttatactatggctcca ttctctacat 840 ctacgctctc cccagatcta gctattcttt tgatatggacaaaatagttt ctacatttta 900 cactgtggta ttccccatgt tgaatctcat gatctacagcctaaggaata aggatgtgaa 960 agaggctctg aaaaaacttc tcccataaat caagattatctccaccagag gagaaacaaa 1020 gacgacctta gatggagtgt tgtgtatttc aaacagagttaccattgtgc tttatcgtga 1080 tcagtcccct tcttgacacg tgagagttac agacatgtacaataagaaaa ttaggaaaat 1140 ttcggacaaa aacatctgaa tatataagaa tttgaattgaatttcctatc tctcttatta 1200 aaaacaaaca taaaccttaa gcccaaaacc tctcctataccttcataaag tgaggaacag 1260 cctacctcat tagcctaaga tttggct 1287 130 1276DNA Homo sapiens misc_feature Incyte ID No 7475235CB1 130 ctctcaaaagaaagctgaaa gaagccacaa attttaacac tgcttttttt ctactaaatt 60 tacagatatgcctattttac caacacaagc aagcggatca cctgaggtca ggtgtatctg 120 tatttttcatagcagagccc tatgaatgaa tcatgtccat tatcaacaca tcatatgttg 180 aaatcaccaccttcttcttg gttgggatgc cagggctaga atatgcacac atctggatct 240 ctatccccatctgcagcatg tatcttattg ctattctagg aaatggcacc attcttttta 300 tcatcaagacagagccctcc ttgcatgggc ccatgtacta ttttctttcc atgttggcta 360 tgtcagacttgggtttgtct ttatcatctc tgcccactgt gttaagcatc ttcctgttca 420 atgcccctgaaacttcttct agtgcctgct ttgcccagga attcttcatt catggattct 480 cagtactggagtcctcagtc ctcctgatca tgtcatttga tagattccta gccatccaca 540 atcctctgagatacacctca atcctgacaa ctgtcagagt tgcccaaata gggatagtat 600 tctcctttaagagcatgctc ctggttcttc ccttcccttt cactttaaga agcttgagat 660 attgcaagaaaaaccaatta tcccattcct actgtctcca ccaggatgtc atgaagttgg 720 cctgttctgacaacagaatt gatgttatct atggcttttt tggagcactc tgccttatgg 780 tagactttattctcattgct gtgtcttaca ccctgatcct caagactgta ccgggaattg 840 catccaaaaaggaggagctt aaggctctca atacttgtgt ttcacacatc tgtgcagtga 900 tcatcttctacctgcccatc atcaacctgg ccgttgtcca ccgctttgcc gggcatgtct 960 ctcccctcattaatgttctc atggcaaatg ttctcctact tgtacctccg ctgatgaaac 1020 caattgtttattgtgtaaaa actaaacaga ttagagtgag agttgtagca aaattgtgtc 1080 aatggaagatttaacagtca tatgtgacag aaaacctgga aatgtctggt aagatattta 1140 aggtaaatttgagaaaccta atatttgaca ccaagaatta tcaacacata tttttatcgt 1200 tatcacagacttattttatt cactctagat actgagaatg ggaataaaac tgtaaccagg 1260 aagtacgttgccttat 1276 131 1097 DNA Homo sapiens misc_feature Incyte ID No7476246CB1 131 tcaaacactg aagaaagaac attgatgata tgaagtcatt tttttcagatctacaaaata 60 ggtttcttct gtgccattag gatgaacaca gttttcactt atgttatcttttaaaaatac 120 ctttaattgt caagctagca ttagaatctc agccaacatc ttccatcttctcttccacat 180 ttttacattc tttcaggatc acaggcctaa gacccatgac ctggtcacctgtcatttggc 240 ctttgtccac ctagtaatgc tcttcactgc aatggagttt ttgtctccagacatgtttga 300 gtcactgaat tttcagaata actttagatg taaagctttc ttctatttgcacaaggtgat 360 gaggggcctc tccatctgca ccacctgcct cctgagcatg ctccaggccattaccatcag 420 cctcagcacc tcctggttgg ttagatttaa acataaattt acaaaatacgatatcctggg 480 cttattcgtt ttttggttta gcaatttgtc tttcagtagt gacatgataatctacactgt 540 aggttattcc aatgacccag ataatttgaa tatcagcaaa tattgcacatttttcccaat 600 gaatgtcctc atcaggacgc tatttcttat gctctcatta tccagagatgccttcttcat 660 aggaatcacg ctgctctcaa gtgtatacat ggtcattctt ttgtccaggcatcagaggca 720 ctcccagcac tttcacagca gcagccttat attaaggact tctctagtgaaaatggccac 780 caagaccatc ctgatgctgg tgaattcctt tgtgctgatg tactcagtggacttcatcct 840 ctcatcatcc acaatgctgt tatgggtaat tggccctgtc acctatggtgtccacaagtt 900 tgtggtcaat gcctatgcca ctgtcagtcc tctggtgcta atcagatctgataaaagaat 960 catcaatatt ctgcaaaagt ttcaatggaa gtgccatcta tttttaacaagttggtgata 1020 aaattttcta aaaattattt ctttgtaatc aattaaatta tacaaaaagcacataatttt 1080 ctttctgatt taaataa 1097 132 1323 DNA Homo sapiensmisc_feature Incyte ID No 7474899CB1 132 tgtgtatcaa gaatccacagctagtttgta atcataattt tccagatcac tgaaagaaag 60 cagtaaaata tatgggaaaatatgacaaca caccgaaatg acaccctctc cactgaagct 120 tcagacttcc tcttgaattgttttgtcaga tcccccagct ggcagcactg gctgtccctg 180 cccctcagcc tccttttcctcttggccgta ggggccaaca ccaccctcct gatgaccatc 240 tggctggagg cctctctgcaccagcccctg tactacctgc tcagcctcct ctccctgctg 300 gacatcgtgc tctgcctcactgtcatcccc aaggtcctga ccatcttctg gtttgacctc 360 aggcccatca gcttccctgcctgcttcctc cagatgtaca tcatgaattg tttcctagcc 420 atggagtctt gcacattcatggtcatggcc tatgatcgtt atgtagccat ctgccaccca 480 ctgagatatc catcaatcatcactgatcac tttgtagtca aggctgccat gtttattttg 540 accagaaatg tgcttatgactctgcccatc cccatccttt cagcacaact ccgttattgt 600 ggaagaaatg tcattgagaactgcatctgt gccaatatgt ctgtttccag actctcctgc 660 gatgatgtca ccatcaatcacctttaccaa tttgctggag gctggactct gctaggatct 720 gacctcatcc ttatcttcctctcctacacc ttcattctgc gagctgtgct gagactcaag 780 gcagagggtg ccgtggcaaaggccctaagc acatgtggct cccacttcat gctcatcctc 840 ttcttcagca ccatccttctggtttttgtc ctcacacatg tggctaagaa gaaagtctcc 900 cctgatgtgc cagtcttgctcaatgttctc caccatgtca ttcctgcagc ccttaacccc 960 atcatttacg gggtgagaacccaagaaatt aagcagggaa tgcagaggtt gttgaagaaa 1020 gggtgctaac aaggaccactggatctctga atatctaaaa taagataatt tattaatcac 1080 ttaatgagtg agtgggctgaaattcatatc tgtgacttat aacctcaaac tgggtacact 1140 agatattgtg tgtgcttttcaaaaacatcg gttttaattt aagtctatct tccttttcac 1200 ccttttctca gaaatattcttggccctctc tcgttttatt ccatgcttat aatcatattt 1260 tgtccaaaac actgacattccttaaagcag attttaaagt gaaaaatgta tgtttctgaa 1320 cac 1323 133 1124 DNAHomo sapiens misc_feature Incyte ID No 7478353CB1 133 atcttctaggaaatacccac tcttacaata acaaacaaaa tctagctgac cacaggattc 60 ttaaagaagaaagtaaagac tttatgcagg aagcaggcct atggctgtag gaaggaacaa 120 cacaattgtgacaaaattca ttctcctggg actttcagac catcctcaaa tgaagatttt 180 ccttttcatgttatttctgg ggctctacct cctgacgttg gcctggaact taagcctcat 240 tgccctcattaagatggact ctcacctgca catgcccatg tacttcttcc tcagtaacct 300 gtccttcctggacatctgct atgtgtcctc caccgcccct aagatgctgt ctgacatcat 360 cacagagcagaaaaccattt cctttgttgg ctgtgccact cagtactttg tcttctgtgg 420 gatggggctgactgaatgct ttctcctggc agctatggcc tatgaccggt atgctgcaat 480 ctgcaaccccttgctttaca cagtcctcat atcccataca ctttgtttaa agatggtggt 540 tggcgcctatgtgggtggat tccttagttc tttcattgaa acatactctg tctatcagca 600 tgatttctgtgggccctata tgatcaacca ctttttctgt gacctccctc cagtcctggc 660 tctgtcctgctctgatacct tcaccagcga ggtggtgacc ttcatagtca gtgttgtcgt 720 tggaatagtgtctgtgctag tggtcctcat ctcttatggt tacattgttg ctgctgttgt 780 gaagatcagctcagctacag gtaggacaaa ggccttcagc acttgtgcct ctcacctgac 840 tgctgtgaccctcttctatg gttctggatt cttcatgtac atgcgaccca gttccagcta 900 ctccctaaacagggacaagg tggtgtccat attctatgcc ttggtgatcc ccgtggtgaa 960 tcccatcatctacagtttta ggaataagga gattaaaaat gccatgagga aagccatgga 1020 aagggaccccgggatttctc acggtggacc attcattttt atgaccttgg gctaatgttt 1080 acaatgaagctgtgagctag gtgaattgtg cagacattta cata 1124 134 1112 DNA Homo sapiensmisc_feature Incyte ID No 7473910CB1 134 gtcatgacat aattatcactcaccccatat tttgctttgg caggaacaat tctcttcaac 60 ccttccatta aaaggaattatgatgatggt tttaaggaat ctgagcatgg agcccacctt 120 tgccctttta ggtttcacagattacccaaa gcttcagatt cctctcttcc ttgtgtttct 180 gctcatgtat gttatcacagtggtaggaaa ccttgggatg atcataataa tcaagattaa 240 ccccaaattt cacactcctatgtacttttt ccttagtcac ctctcttttg ttgatttttg 300 ttactcttcc attgtcactcccaagctgct tgagaacttg gtaatggcag ataaaagcat 360 cttctacttt agctgcatgatgcagtactt cctgtcctgc actgctgtgg tgacagagtc 420 tttcttgctg gcagtgatggcctatgaccg ctttgtggcc atctgcaatc ctctgcttta 480 tacagtggcc atgtcacagaggctctgtgc cctgctggtg gctgggtcat atctctgggg 540 catgtttggc cccttggtactcctttgtta tgctctccgg ttaaacttct ctggacctaa 600 tgtaatcaac cacttcttttgtgagtatac tgctctcatc tctgtgtctg gctctgatat 660 actcatcccc cacctgctgcttttcagctt cgccaccttc aatgagatgt gtacactact 720 gatcatcctc acttcctatgttttcatttt tgtgactgta ctaaaaatcc gttctgttag 780 tgggcgccac aaagccttctccacctgggc ctcccacctg acttctatca ccatcttcca 840 tgggaccatc cttttcctttactgtgtacc caactccaaa aactctcggc aaacagtcaa 900 agtggcctct gtattttacacagttgtcaa ccccatgctg aaccctctga tctacagcct 960 aaggaataaa gacgtgaaggatgctttctg gaagttaata catacacaag ttccatttca 1020 ctgaaccagt ctcaaaagttgttttcaatc caaatgaaca acccaaacag aggctacaat 1080 gtttctaaag cctagagcatatatttatat ga 1112 135 633 DNA Homo sapiens misc_feature Incyte ID No7476047CB1 135 atgttttttc ttcatggatt cacttttatg gaatctggag tgctggtggctacagccttt 60 gaccgttatg tggccatctg tgatcctctg aggtacacta ccattctcactaattccaga 120 atcattcaaa tgggtcttct gatgattaca cgtgctatag tactaatattaccactactt 180 ttgctcctta agcctctcta tttctgtaga atgaatgccc tttctcactcctattgttac 240 catccagatg tgattcaatt agcatgttca gacattcggg caaatagcatctgtggatta 300 attgatctca tcctgaccac tggaatagat acaccatgca ttgtcctgtcatatatctta 360 attattcgct ttgtcctcag aattgcctcc cctgaagaat ggcacaaggtcttcagcacc 420 tgtgtctccc acgtgggagc agttgctttc ttctacatcc acatgctgagcctgtccttg 480 gtgtatcgct atggtcggtc agcccccaga gtagtccatt cagtgatggctaacgtatac 540 ctgcttttac cccctgtgct caaccccatc atctacagtg taaaaacaaaacaaatccgc 600 aaggctatgc tcagtctgct gcttacaaaa tga 633 136 2979 DNAHomo sapiens misc_feature Incyte ID No 7289994CB1 136 taacactgaagccatggcta gctggaggca ccatatcctc ctagttcagc ttctagaaga 60 taattcatctacaccagttc tacaagcatg ctttattaat aaagcgaata tttctccagc 120 acagaatcttagagctggtg caggtttgcc attgtgtcct ggtgtatgtg ctatcaatgt 180 aggctgtgttctgatgtctt ttttgatttc acaggaactg acaatggcga agcccttccc 240 gaatccatcccatcagctcc tgggacactg cctcatttca tagaggagcc agatgatgct 300 tatattatcaagagcaaccc tattgcactc aggtgcaaag cgaggccagc catgcagata 360 ttcttcaaatgcaacggcga gtgggtccat cagaacgagc acgtctctga agagactctg 420 gacgagagctcaggtttgaa ggtccgcgaa gtgttcatca atgttactag gcaacaggtg 480 gaggacttccatgggcccga ggactattgg tgccagtgtg tggcgtggag ccacctgggt 540 acctccaagagcaggaaggc ctctgtgcgc atagcctatt tacggaaaaa ctttgaacaa 600 gacccacaaggaagggaagt tcccattgaa ggcatgattg tactgcactg ccgcccacca 660 gagggagtccctgctgccga ggtggaatgg ctgaaaaatg aagagcccat tgactctgaa 720 caagacgagaacattgacac cagggctgac cataacctga tcatcaggca ggcacggctc 780 tcggactcaggaaattacac ctgcatggca gccaacatcg tggctaagag gagaagcctg 840 tcggccactgttgtggtcta cgtgaatgga ggctggtctt cctggacaga gtggtcagcc 900 tgcaatgttcgctgtggtag aggatggcag aaacgttccc ggacctgcac caacccagct 960 cctctcaatggtggggcctt ttgtgaggga atgtcagtgc agaaaataac ctgcacttct 1020 ctttgtcctgtggatgggag ctgggaagtg tggagcgaat ggtccgtctg cagtccagag 1080 tgtgaacatttgcggatccg ggagtgcaca gcaccacccc cgagaaatgg gggcaaattc 1140 tgtgaaggtctaagccagga atctgaaaac tgcacagatg gtctttgcat cctaggcatt 1200 gagaatgccagcgacattgc tttgtactcg ggcttgggtg ctgccgtcgt ggccgttgca 1260 gtcctggtcattggtgtcac cctttacaga cggagccaga gtgactatgg cgtggacgtc 1320 attgactcttctgcattgac aggtggcttc cagaccttca acttcaaaac agtccgtcaa 1380 ggtaactccctgctcctgaa ttctgccatg cagccagatc tgacagtgag ccggacatac 1440 agcggacccatctgtctgca ggaccctctg gacaaggagc tcatgacaga gtcctcactc 1500 tttaaccctttgtcggacat caaagtgaaa gtccagagct cgttcatggt ttccctggga 1560 gtgtctgagagagctgagta ccacggcaag aatcattcca ggacttttcc ccatggaaac 1620 aaccacagctttagtacaat gcatcccaga aataaaatgc cctacatcca aaatctgtca 1680 tcactccccacaaggacaga actgaggaca actggtgtct ttggccattt aggggggcgc 1740 ttagtaatgccaaatacagg ggtgagctta ctcataccac acggtgccat cccagaggag 1800 aattcttgggagatttatat gtccatcaac caaggtgaac ccagcctcca gtcagatggc 1860 tctgaggtgctcctgagtcc tgaagtcacc tgtggtcctc cagacatgat cgtcaccact 1920 ccctttgcattgaccatccc gcactgtgca gatgtcagtt ctgagcattg gaatatccat 1980 ttaaagaagaggacacagca gggcaaatgg gaggaagtga tgtcagtgga agatgaatct 2040 acatcctgttactgcctttt ggaccccttt gcgtgtcatg tgctcctgga cagctttggg 2100 acctatgcgctcactggaga gccaatcaca gactgtgccg tgaagcaact gaaggtggcg 2160 gtttttggctgcatgtcctg taactccctg gattacaact tgagagttta ctgtgtggac 2220 aataccccttgtgcatttca ggaagtggtt tcagatgaaa ggcatcaagg tggacagctc 2280 ctggaagaaccaaaattgct gcatttcaaa gggaatacct ttagtcttca gatttctgtc 2340 cttgatattcccccattcct ctggagaatt aaaccattca ctgcctgcca ggaagtcccg 2400 ttctcccgcgtgtggtgcag taaccggcag cccctgcact gtgccttctc cctggagcgt 2460 tatacgcccactaccaccca gctgtcctgc aaaatctgca ttcggcagct caaaggccat 2520 gaacagatcctccaagtgca gacatcaatc ctagagagtg aacgagaaac catcactttc 2580 ttcgcacaagaggacagcac tttccctgca cagactggcc ccaaagcctt caaaattccc 2640 tactccatcagacagcggat ttgtgctaca tttgataccc ccaatgccaa aggcaaggac 2700 tggcagatgttagcacagaa aaacagcatc aacaggaatt tatcttattt cgctacacaa 2760 agtagcccatctgctgtcat tttgaacctg tgggaagctc gtcatcagca tgatggtgat 2820 cttgactccctggcctgtgc ccttgaagag attgggagga cacacacgaa actctcaaac 2880 atttcagaatcccagcttga tgaagccgac ttcaactaca gcaggcaaaa tggactctag 2940 tccacttcctcccatgagac agagtgatgg ccagcttgg 2979 137 1191 DNA Homo sapiensmisc_feature Incyte ID No 7482840CB1 137 atgatgatag ccacataaatgctttgttct ctcaaaagaa agctgaaaga agccacaaat 60 tttaacactg ctttttttctactaaattta cagatattcc tattttacca acacaagcat 120 ctgtattttt catagcagagccctatgaat gaatcatgtc cattatcaac acatcatatg 180 ttgaaatcac caccttcttcttggttggga tgccagggct agaatatgca cacatctgga 240 tctctatccc catctgcagcatgtatctta ttgctattct aggaaatggc accattcttt 300 ttatcatcaa gacagagccctccttgcatg agcccatgta ctattttctt tccatgttgg 360 ctatgtcaga cttgggtttgtctttatcat ctctgcccac tgtgttaagc atcttcctgt 420 tcaatgctcc tgaaatttcatccaatgcct gctttgccca ggaattcttc attcatggat 480 tctcagtact ggagtcctcagtcctcctga tcatgtcatt tgatagattc ctagccatcc 540 acaaccctct gagatacacctcaatcctga caactgtcag agttgcccaa atagggatag 600 tattctcctt taagagcatgctcctggttc ttcccttccc tttcacttta agaaacttga 660 gatattgcaa gaaaaaccaattatcccatt cctactgtct ccaccaggat gtcatgaagt 720 tggcctgttc tgacaacagaattgatgtta tctatggctt ttttggagca ctctgcctta 780 tggtagactt tattctcattgctgtgtctt acaccctgat cctcaagact gtactgggaa 840 ttgcatccaa aaaggagcagcttaaggctc tcaatacttg tgtttcacac atctgtgcag 900 tgatcatctt ctacctgcccatcatcaacc tggccgttgt ccaccgcttt gcccggcatg 960 tctctcccct cattaatgttctcatggcaa atgttctcct acttgtacct ccactgacga 1020 acccaattgt ttattgtgtaaaaactaaac agattagagt gagagttgta gcaaaattgt 1080 gtcaacggaa gatttaacagtcatatgtga cagaaaacct ggaaatgtct ggtaagatat 1140 ttaaggtaaa tttgagaaacctaatatttg acaccaagaa ttatcaacac a 1191 138 1385 DNA Homo sapiensmisc_feature Incyte ID No 55093631CB1 138 gtctgattgg atatctgcgggaatgctccc tgtgttttaa cccagtgtca cgatccattg 60 taaaacgacg gacaaagaataagtattctc tatcacgtaa tttaataatg tatctattcg 120 tatccggtag acacatctcggtcgttgcat gttgctacca ttattactaa tttaagcctt 180 agttcatttc agacaggttctattgttcgg atgacaaatt atatggtcac tttatcttca 240 ggaggcaata attataaattacgttgaaag tctgagagtt acgtcaagtt tctctatcct 300 taatcaccct ctgctcttgagcgggctgag atttatgcca tctggctctg ccatgatcat 360 tttcaacctg agcagttacaatccagggcc cttcatcctg gtagggatcc caggcctgga 420 gcaattccat gtgtggattggaattccctt ctgtatcatc tacattgtag ctgttgtggg 480 aaactgcatc cttctctacctcattgtggt ggagcatagt cttcatgaac ccatgttctt 540 ctttctctcc atgctggccatgactgacct catcttgtcc acagctggtg tgcctaaagc 600 actcagtatc ttttggctaggggctcgcgt aatcacattc ccaggatgcc ttacacaaat 660 gttcttcctt cactataactttgtcctgga ttcagccatt ctgatggcca tggcatctga 720 tcactatgta gctatctgttctcccttgag atataccacc atcttgactc ccaagaccat 780 catcaagagt gctatgggcatctcctttcg aagcttctgc atcatcctgc cagatgtatt 840 cttgctgaca tgcctgcctttctgcaggac acgcatcata ccccacacat actgtgagca 900 tataggtgtt gcccagctcgcctgtgctga tatctccatc aacttctggt atggcttttg 960 tgttcccatc atgacggtcatctcagatgt gattctcatt gctgtttcct acgcacacat 1020 cctctgtgct gtctttggccttccctccca agatgcctgc cagaaagccc tcggcacttg 1080 tggttctcat gtctgtgtcatcctcatgtt ttatacacct gcctttttct ccatcctcgc 1140 ccatcgcttt ggacacaatgtctctcgcac cttccacatc atgtttgcca atctctacat 1200 tgttatccca cctgcactcaaccccatggt ttacggagtg aagaccaagc agatcagaga 1260 taaggttata cttttgttttctaagggtac aggatgatgt tttactagga taagtttata 1320 gtgtacagaa atgtagaaagagtgaaaggt tttccacccc agagggaggt tctgtaacgc 1380 agtcc 1385 139 1203 DNAHomo sapiens misc_feature Incyte ID No 7474992CB1 139 tctttggtttcaacagcaat tgattggctt taagtcacag tatacttatg aggcaaaaat 60 taataataacattaatttaa aaatagcttt gtaaatccta ataccataag agattatttg 120 taatgctaggatccaaacca agagttcatt tgtatatttt gccctgtgcc tctcaacagg 180 tttctaccatgggtgacagg ggaacaagca atcactcaga aatgactgac ttcattcttg 240 caggcttcagggtacgccca gagctccaca ttctcctctt cctgctattt ttgtttgttt 300 atgccatgatccttctaggg aatgttggga tgatgaccat tattatgact gatcctcggc 360 tgaacacaccaatgtatttt ttcctaggca atctctcctt cattgatctt ttctattcat 420 ctgttattgaacccaaggct atgatcaact tctggtctga aaacaagtct atctcctttg 480 caggctgtgtggcccagctc tttctctttg ccctcctcat tgtgactgag ggatttctcc 540 tggcggccatggcttatgac cgctttattg ccatctgcaa ccctctgctc tactctgttc 600 aaatgtccacacgtctgtgt actcagttgg tggctggttc ctatttttgt ggctgcatta 660 gctcagttattcagactagc atgacattta ctttatcttt ttgcgcttct cgggctgttg 720 accacttttactgtgattct cgcccacttc agagactgtc ttgttctgat ctctttatcc 780 atagaatgatatctttttcc ttatcatgta ttattatctt gcctactatc atagtcatta 840 tagtatcttacatgtatatt gtgtccacag ttctaaagat acattctact gagggacata 900 agaaggccttctccacctgc agctctcacc tgggagttgt gagtgtgctg tatggtgctg 960 tcttttttatgtatctcact cctgacagat ttcctgagct gagtaaagtg gcatccttat 1020 gttactccctagtcactccc atgttgaatc ctttgattta ctctctgagg aacaaagatg 1080 tccaagaggctctaaaaaaa tttctagaga agaaaaatat tattctttga ttattatttc 1140 tctttcaccaattttattgt ggctatttat ttaatacacc tgtgttcatt aataaaagtt 1200 act 1203 1401300 DNA Homo sapiens misc_feature Incyte ID No 7476244CB1 140caagaatatg tatttgacct ctaaatttag aatctatttc tttttttctt ttgcagatta 60actagttcta atctgtggtt tcttcacatc aactgaaaca atgcagcaaa ataacagtgt 120gcctgaattc atactgttag gattaacaca ggatcccttg aggcagaaaa tagtgtttgt 180aatcttctta attttctata tgggaactgt ggtggggaat atgctcatta ttgtgaccat 240caagtccagc cggacactag gaagccccat gtacttcttt ctattttatt tgtcctttgc 300agattcttgc ttttcaactt ccacagcccc tagattaatt gtggatgctc tctctgaaaa 360gaaaattata acctacaatg agtgcatgac acaagtcttt gcactacatt tatttggctg 420catggagatc tttgtcctca ttctcatggc tgttgatcgc tatgtggcca tctgtaagcc 480cttgcgttac ccaaccatca tgagccagca ggtctgcatc atcctgattg ttcttgcctg 540gatagggtct ttaatacact ctacagctca gattatcctg gccttaagat tgcctttctg 600tggaccctat ttgattgatc attattgctg tgatttgcag cccttgttga aacttgcctg 660catggacact tacatgatca acctgctgtt ggtgtctaac agtggggcaa tttgctcaag 720tagtttcatg attttgataa tttcatatat tgtcatcttg cattcactga gaaaccacag 780tgccaaaggg aagaaaaagg ctctctccgc ttgcacgtct cacataattg tagtcatctt 840attctttggc ccatgtatat tcatatatac acgccccccg accactttcc ccatggacaa 900gatggtggca gtattttata ctattggaac accctttctc aatccactca tctacacact 960gaggaatgca gaagtgaaaa atgccatgag aaagttatgg catggcaaaa ttatttcaga 1020aaacaaagga taaattgagg gcctgacctg attacttttt cagtcaaatc atgatttaac 1080agagtaagta tagacagcaa ataggaaagt acctgaatgc tgtgggaata atatatcatc 1140gtatctaagt ttgtgggttc ctatgttttc tagttaacag gagttgtgac taccaagaca 1200ttgtcttttg tgccagaact aggtagaata tagattaatt caggtgatta cctaccagta 1260gtcttttctt ttcagattat cttcctttcc agccatgcat 1300 141 957 DNA Homosapiens misc_feature Incyte ID No 7487604CB1 141 atggacaaga taaaccagacatttgtgaga gaattcattc ttctgggact ctctggttac 60 cccaaacttg agatcattttctttgctctg attctagtta tgtacgtagt gattctaatt 120 ggcaatggtg ttctgatcatagcaagcatc ttggattctc gtcttcacat gcccatgtac 180 ttcttcctgg gcaacctctctttcctggat atctgctata caacctcctc cattccctca 240 acactggtga gcttaatctcaaagaaaaga aacatttcct tctctggatg tgcagtgcag 300 atgttctttg ggtttgcaatggggtcaaca gaatgtttcc tccttggcat gatggcattt 360 gatcgttatg tggccatctgtaaccctctg agatacccca tcatcatgaa caaggtggtg 420 tatgtactgc tgacttctgtatcatggctt tctggtggaa tcaattcaac tgtgcaaaca 480 tcacttgcca tgcgatggcctttctgtggg aacaatatta ttaatcattt cttatgcgag 540 atcttagctg tcctaaaattagcttgttct gatatatctg tcaatattgt taccctagca 600 gtgtcaaata ttgctttcctagttcttcct ctgctcgtga tttttttctc ctatatgttc 660 atcctctaca ccatcttgcgaacgaactcg gccacaggaa gacacaaggc attttctaca 720 tgctcagctc acctgactgtggtgatcata ttttatggta ccatcttctt tatgtatgca 780 aaacctaagt cccaggacctccttgggaaa gacaacttgc aagctacaga ggggcttgtt 840 tccatgtttt atggggttgtgacccccatg ttaaacccca taatctatag cttgagaaat 900 aaagatgtaa aagctgctataaaatatttg ctgagcagga aagctattaa ccagtaa 957 142 1300 DNA Homo sapiensmisc_feature Incyte ID No 7483200CB1 142 aaagatatac acatacatttttttataaaa ggtttatgac aacattttat gtgagccact 60 gcatataact ttgttgttttctatttcaca tgtgcataaa ttcgatcaca tgttgggtat 120 ttgctctttg atgttactgtaatgtactta ttctattttt gtgtctctgt ctggaacaga 180 ttttcttata aaaactaatggaaaagaaca acctcacagc agtgactcaa ttcatcctga 240 tgggtattac tgagcgccctgaactacagg ccccattgtt tggattgttc ctagtcatct 300 acttgagctc aatgtttggcaacttgggca tgatcattct aaccacagtg gactccaaat 360 tgcaaacacc catgtactttttcattagac acctggctat cacagacctt ggttattcta 420 cagctgtggg acctaagatgttggtaaatt ttgttgtaga tttgaacata atctcctata 480 atctttgtgc tacacagctagctttttttc ttgtgtttat aattagtgag cttttgattc 540 tgtctgcaat gtcctatgaccgctatgtgg ccatctgtaa gcccctcctc tacactgtca 600 tcatgtcgca aagggtgtgtcaggtgctgg tggcaatccc ctatttgtac tgcacatttg 660 tttctcttct agttaccataaagattttta cattgtcttt ctgtgggtat aatgtcatca 720 gtcatttcta ctgtgacagtcttcccttgt tatctttgat ctgttcaaac acaaatgaaa 780 ttgaaatgat tattctggtcttagcagctt ttaatttgat atcctccctt ctagtggtcc 840 ttgtttctta cctgttcatccttatagcca ttctcagaat gaactcggct gagggcagac 900 gcaaggcttt ctcaacctgtggttcccacc tgacagtggt cactgtcttc tatggtactt 960 taatatttat gtatgtgcagcctcagtcca gtcactcttt tgacacggat aaagtggctt 1020 ccatctttta taccctgattatacccatgt taaaccccat gatatacagt ttgaggaaca 1080 aagatgtaaa atatgcacttcaaaggtcat tgaaaaagat atacagcata ctctcataaa 1140 tattacatac aagaggatttctactaacca gaattgaatg aacctttcct atgattttgt 1200 cagaatgttt atcctggaaataatgactct attgtatatt taaagatagc cctgctttgt 1260 accaacccat ttcatatttctctgaataca tcactaaaaa 1300 143 1185 DNA Homo sapiens misc_feature IncyteID No 7476069CB1 143 atttaggtga cactatagaa gagcccagtg tgctggaaagtggaaaactc acctctaaga 60 ataagtagaa gtggatttta aacttgtttc taatataattttaaatttct acataaaatt 120 attctccttt cttcagtttt tagtctgaga agacactctggagtgggaga cttttaggtt 180 taacaaatga aaaaaaaaga ttgtttaggc caaagggaaaatagtggcta atgaaatagc 240 cataagcagt aagcagagat caactcagaa actttctctttttgaataaa aatagaataa 300 agtgctatat cattttattc aagcccaaaa gctcaggaaacagaaggaaa tagagctcct 360 aaaatgaatg gagtttgttt catagcctaa gaaagggttatgaggtagct cttctttctc 420 aagcccacac ttactaggga ctttataagt aatgatcaaatgaacaatgc ttcttactcc 480 tagggtggac aactactgcc tggaatctct atgttctcctgcaacaccag cacttctggt 540 cagtctacct tcctcctcac tggttttcca ggcctggaagcctctcatca ttgggtttcc 600 atccccatca acctcttctg tgtggtttcc atcctgggtaataatatcat cctcttcctg 660 atccacacag atccagcctt acatgaaccc atgtatatcttcctgtccat gttggcagcc 720 tctgatctgg gcctctgtgc ctctaccttc cccactatggtgcgtctctt ctggctggga 780 gctcgtgagc tgccctttga tctctgtgca gcacagatgttcttcatcca taccttcacc 840 tatgtggagt ccggtgtact gctggccatg gccttcgatcgctttattgc catccgggac 900 cctctgcatt atgccataat cattacctgc tcagtcacagccgaggtggg aactgccatt 960 ctggtgaggg ctgttctgct caacctcccg ggacctatcctcctgcagca gctgctcttt 1020 cccaagatca gcgctctctg tcactgctac tgcctgcactgtgaccttgt ggggttggcc 1080 tgctcagaca cccagatcaa tagcctggtt ggcctggtttccatcctctt ctcactgtgc 1140 cttgactcct tcctcatcat gctttcatat gccctgatcctatga 1185 144 1227 DNA Homo sapiens misc_feature Incyte ID No7472453CB1 144 ttttcataga gagaaaacac tgatatttgt tttctataga aacaaacactgatagaattt 60 gactttttct ctctcatctc cacagatttc tcagagaaga atgggtgtaaaaaaccattc 120 cacagtgact gagtttcttc tttcaggatt aactgaacaa gcagagcttcagctgcccct 180 cttctgcctc ttcttaggaa tttacacagt tactgtggtg ggaaacctcagcatgatctc 240 aattattagg ctgaatcgtc aacttcatac ccccatgtac tatttcctgagtagtttgtc 300 ttttttagat ttctgctatt cttctgtcat tacccctaaa atgctatcagggtttttatg 360 cagagataga tccatctcct attctggatg catgattcag ctgttttttttctgtgtttg 420 tgttatttct gaatgctaca tgctggcagc catggcctgc gatcgctacgtggccatctg 480 cagcccactg ctctacaggg tcatcatgtc ccctagggtc tgttctctgctggtggctgc 540 tgtcttctca gtaggtttca ctgatgctgt gatccatgga ggttgtatactcaggttgtc 600 tttctgtgga tcaaacatca ttaaacatta tttctgtgac attgtccctcttattaaact 660 ctcctgctcc agcacttata ttgatgagct tttgattttt gtcattggtggatttaacat 720 ggtggccaca agcctaacaa tcattatttc atatgctttt atcctcaccagcatcctgcg 780 catccactct aaaaagggca ggtgcaaagc gtttagcacc tgtagctcccacctgacagc 840 tgttcttatg ttttatgggt ctctgatgtc catgtatctc aaacctgcttctagcagttc 900 actcacccag gagaaagtat cctcagtatt ttataccact gtgattctcatgttgaatcc 960 cttgatatat agtctgagga acaatgaagt aagaaatgct ctgatgaaacttttaagaag 1020 aaaaatatct ttatctccag gataaatatg ctctttatta agatctatttctgtattcat 1080 aatcatgatt atatgtatat atttatacct tgactattta aaagtaatttgaggtccagg 1140 tacggtgact tacgcctgta atcccagcac tttgggaggc cgagttgggtggatcacgag 1200 gtccggtgtt caagaccagc ctggcca 1227 145 1498 DNA Homosapiens misc_feature Incyte ID No 5492483CB1 145 gccaaacatg taagtgaatatttatttctg aatgccatgt cattttactt tctcttaagg 60 gaagtcaaca ttattacatgaacatttcag atgtcatctc ctttgatatt ttggtttcag 120 ccatgaaaac aggaaatcaaagttttggga cagattttct acttgttggt cttttccaat 180 atggctggat aaactctcttctctttgtcg tcattgccac cctctttaca gttgctctga 240 caggaaatat catgctgatccacctcattc gactgaacac cagactccac actccaatgt 300 actttctgct cagtcagctctccatcgttg acctcatgta catctccacc acagtgccca 360 agatggcagt cagcttcctctcacagagta agaccattag atttttgggc tgtgagattc 420 aaacgtatgt gttcttggcccttggtggaa ctgaagccct tctccttggt tttatgtctt 480 atgatcgcta tgtagctatctgtcaccctt tacattatcc tatgcttatg agcaagaaga 540 tctgctgcct catggttgcatgtgcatggg ccagtggttc tatcaatgct ttcatacata 600 cattgtatgt gtttcagcttccattctgta ggtctcggct cattaaccac tttttctgtg 660 aagttccagc tctactatcattggtgtgtc aggacacctc ccagtatgag tatacagtcc 720 tcctgagtgg acttattatcttgctactac cattcctagc cattctggct tcctatgctc 780 gtgtgcttat tgtggtattccagatgagct caggaaaagg acaggcaaaa gctgtttcca 840 cttgttcctc ccacctgattgtggcaagcc tgttctatgc aaccactctc tttacctaca 900 caaggccaca ctccttgcgttccccttcac gggataaggc ggtggcagta ttttacacca 960 ttgtcacacc tctactgaacccatttatct acagcctgag aaataaggaa gtgacggggg 1020 cagtgaggag actgttgggatattggatat gctgtagaaa atatgacttc agatctctgt 1080 attgattgag cattaacaacataaaaagct gttcctgaaa actatctgga aagatataaa 1140 tatgtgtttt ctgtatagaagtcacaaaaa cagtgtttat caatcttgtt taacttgtaa 1200 agcaatagaa ttcaggcttcttaaatctgt gttcccctgg cattttaatg cttttacttg 1260 ccctcttgaa tactctgaaatgtgaaccat aaaaataaaa tctacttaaa catttaacct 1320 caagataatc tatataacaaccaaagttaa cagagagaaa aatgcataat tcatttattc 1380 cttctttcac tcaggtgttttaatgcttta atttgtgtgt gacactgtta cagacactgg 1440 tcatgtgaga gtaaacaaaaatgaaagctg acagaaatct ctgctgatcg gcaaactt 1498 146 1218 DNA Homo sapiensmisc_feature Incyte ID No 7472079CB1 146 aagtgaaagg gatacttttcaaagcaattt gtaaaaataa cctcttgtat ctgcccataa 60 acatagtcat cagaagcctactcagctcat gattcagcct atggcgtcac ccagcaacag 120 ctccactgtc ccagtctctgaattcctcct cacctgcttc cccaacttcc agagttggca 180 gcactggctc tccctgcccctcagccttct cttcctcctg gccatgggag ctaacaccac 240 cctcctgatc accatccagctggaggcctc tctgcaccag cccctgtact acctgctcag 300 cctcctctcc ctgctggacatcgtgctctg cctcaccgtc atccccaagg tcctggccat 360 cttctggtat gatcttaggtcgatcagctt ccctgcctgc ttcctccaga tgttcatcat 420 gaacagtttc ctccccatggagtcctgcac gtttatggtc atggcctatg accgttatgt 480 ggccatctgc cacccactgcggtacccatc catcatcact aatcaatttg tggccaaagc 540 tagtgtcttc attgtggtgcggaatgcgct tcttactgca cccattccta tcctcacttc 600 cctgctccat tactgtggggaaaatgtcat tgagaactgc atctgtgcca acttgtctgt 660 gtccaggctc tcctgtgataatttcaccct taacagaatc taccaatttg tggctggttg 720 gaccttgctg ggctcagatttattcctcat cttcctctct tacaccttca ttctaagagc 780 tgtgcttaga ttcaaagcagagggggcggc agtgaaggcc ctgagcacat gtggctccca 840 cttcatcctc attcttttcttcagcaccat actgctggtt gtggtgttga caaacgtggc 900 cagaaagaag gtccccatggacatcctgat cctgctgaac gtccttcatc accttattcc 960 tcctgcgttg aaccctattgtgtatggggt tcggaccaaa gagataaaac agggaattca 1020 gaagttactg cagagagggaggtgaatatg taaagcattt ctaatacctc ctgttcttcc 1080 tcttcagtga ttttacctaggcagcgaagt agagaaatgt cagttagtga gtgtttattg 1140 catgcactga ggctcccttcattactgaac cagattcctt cctttacttt ccttgcctag 1200 ttcaggtgga ggtaggca1218

What is claimed is:
 1. An isolated polypeptide selected from the groupconsisting of: a) a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73, b) a polypeptidecomprising a naturally occurring amino acid sequence at least 90%identical to an amino acid sequence selected from the group consistingof SEQ ID NO:1-73, c) a biologically active fragment of a polypeptidehaving an amino acid sequence selected from the group consisting of SEQID NO:1-73, and d) an immunogenic fragment of a polypeptide having anamino acid sequence selected from the group consisting of SEQ IDNO:1-73.
 2. An isolated polypeptide of claim 1 comprising an amino acidsequence selected from the group consisting of SEQ ID NO:1-73.
 3. Anisolated polynucleotide encoding a polypeptide of claim
 1. 4. Anisolated polynucleotide encoding a polypeptide of claim
 2. 5. Anisolated polynucleotide of claim 4 comprising a polynucleotide sequenceselected from the group consisting of SEQ ID NO:74-146.
 6. A recombinantpolynucleotide comprising a promoter sequence operably linked to apolynucleotide of claim
 3. 7. A cell transformed with a recombinantpolynucleotide of claim
 6. 8. A transgenic organism comprising arecombinant polynucleotide of claim
 6. 9. A method of producing apolypeptide of claim 1, the method comprising: a) culturing a cell underconditions suitable for expression of the polypeptide, wherein said cellis transformed with a recombinant polynucleotide, and said recombinantpolynucleotide comprises a promoter sequence operably linked to apolynucleotide encoding the polypeptide of claim 1, and b) recoveringthe polypeptide so expressed.
 10. A method of claim 9, wherein thepolypeptide comprises an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73.
 11. An isolated antibody whichspecifically binds to a polypeptide of claim
 1. 12. An isolatedpolynucleotide selected from the group consisting of: a) apolynucleotide comprising a polynucleotide sequence selected from thegroup consisting of SEQ ID NO:74-146, b) a polynucleotide comprising anaturally occurring polynucleotide sequence at least 90% identical to apolynucleotide sequence selected from the group consisting of SEQ IDNO:74-146, c) a polynucleotide complementary to a polynucleotide of a),d) a polynucleotide complementary to a polynucleotide of b), and e) anRNA equivalent of a)-d).
 13. An isolated polynucleotide comprising atleast 60 contiguous nucleotides of a polynucleotide of claim
 12. 14. Amethod of detecting a target polynucleotide in a sample, said targetpolynucleotide having a sequence of a polynucleotide of claim 12, themethod comprising: a) hybridizing the sample with a probe comprising atleast 20 contiguous nucleotides comprising a sequence complementary tosaid target polynucleotide in the sample, and which probe specificallyhybridizes to said target polynucleotide, under conditions whereby ahybridization complex is formed between said probe and said targetpolynucleotide or fragments thereof, and b) detecting the presence orabsence of said hybridization complex, and, optionally, if present, theamount thereof.
 15. A method of claim 14, wherein the probe comprises atleast 60 contiguous nucleotides.
 16. A method of detecting a targetpolynucleotide in a sample, said target polynucleotide having a sequenceof a polynucleotide of claim 12, the method comprising: a) amplifyingsaid target polynucleotide or fragment thereof using polymerase chainreaction amplification, and b) detecting the presence or absence of saidamplified target polynucleotide or fragment thereof, and, optionally, ifpresent, the amount thereof.
 17. A composition comprising a polypeptideof claim 1 and a pharmaceutically acceptable excipient.
 18. Acomposition of claim 17, wherein the polypeptide comprises an amino acidsequence selected from the group consisting of SEQ ID NO:1-73.
 19. Amethod for treating a disease or condition associated with decreasedexpression of functional GCREC, comprising administering to a patient inneed of such treatment the composition of claim
 17. 20. A method ofscreening a compound for effectiveness as an agonist of a polypeptide ofclaim 1, the method comprising: a) exposing a sample comprising apolypeptide of claim 1 to a compound, and b) detecting agonist activityin the sample.
 21. A composition comprising an agonist compoundidentified by a method of claim 20 and a pharmaceutically acceptableexcipient.
 22. A method for treating a disease or condition associatedwith decreased expression of functional GCREC, comprising administeringto a patient in need of such treatment a composition of claim
 21. 23. Amethod of screening a compound for effectiveness as an antagonist of apolypeptide of claim 1, the method comprising: a) exposing a samplecomprising a polypeptide of claim 1 to a compound, and b) detectingantagonist activity in the sample.
 24. A composition comprising anantagonist compound identified by a method of claim 23 and apharmaceutically acceptable excipient.
 25. A method for treating adisease or condition associated with overexpression of functional GCREC,comprising administering to a patient in need of such treatment acomposition of claim
 24. 26. A method of screening for a compound thatspecifically binds to the polypeptide of claim 1, the method comprising:a) combining the polypeptide of claim 1 with at least one test compoundunder suitable conditions, and b) detecting binding of the polypeptideof claim 1 to the test compound, thereby identifying a compound thatspecifically binds to the polypeptide of claim
 1. 27. A method ofscreening for a compound that modulates the activity of the polypeptideof claim 1, the method comprising: a) combining the polypeptide of claim1 with at least one test compound under conditions permissive for theactivity of the polypeptide of claim 1, b) assessing the activity of thepolypeptide of claim 1 in the presence of the test compound, and c)comparing the activity of the polypeptide of claim 1 in the presence ofthe test compound with the activity of the polypeptide of claim 1 in theabsence of the test compound, wherein a change in the activity of thepolypeptide of claim 1 in the presence of the test compound isindicative of a compound that modulates the activity of the polypeptideof claim
 1. 28. A method of screening a compound for effectiveness inaltering expression of a target polynucleotide, wherein said targetpolynucleotide comprises a sequence of claim 5, the method comprising:a) exposing a sample comprising the target polynucleotide to a compound,under conditions suitable for the expression of the targetpolynucleotide, b) detecting altered expression of the targetpolynucleotide, and c) comparing the expression of the targetpolynucleotide in the presence of varying amounts of the compound and inthe absence of the compound.
 29. A method of assessing toxicity of atest compound, the method comprising: a) treating a biological samplecontaining nucleic acids with the test compound, b) hybridizing thenucleic acids of the treated biological sample with a probe comprisingat least 20 contiguous nucleotides of a polynucleotide of claim 12 underconditions whereby a specific hybridization complex is formed betweensaid probe and a target polynucleotide in the biological sample, saidtarget polynucleotide comprising a polynucleotide sequence of apolynucleotide of claim 12 or fragment thereof, c) quantifying theamount of hybridization complex, and d) comparing the amount ofhybridization complex in the treated biological sample with the amountof hybridization complex in an untreated biological sample, wherein adifference in the amount of hybridization complex in the treatedbiological sample is indicative of toxicity of the test compound.
 30. Adiagnostic test for a condition or disease associated with theexpression of GCREC in a biological sample, the method comprising: a)combining the biological sample with an antibody of claim 11, underconditions suitable for the antibody to bind the polypeptide and form anantibody:polypeptide complex, and b) detecting the complex, wherein thepresence of the complex correlates with the presence of the polypeptidein the biological sample.
 31. The antibody of claim 11, wherein theantibody is: a) a chimeric antibody, b) a single chain antibody, c) aFab fragment, d) a F(ab′)₂ fragment, or e) a humanized antibody.
 32. Acomposition comprising an antibody of claim 11 and an acceptableexcipient.
 33. A method of diagnosing a condition or disease associatedwith the expression of GCREC in a subject, comprising administering tosaid subject an effective amount of the composition of claim
 32. 34. Acomposition of claim 32, wherein the antibody is labeled.
 35. A methodof diagnosing a condition or disease associated with the expression ofGCREC in a subject, comprising administering to said subject aneffective amount of the composition of claim
 34. 36. A method ofpreparing a polyclonal antibody with the specificity of the antibody ofclaim 11, the method comprising: a) immunizing an animal with apolypeptide consisting of an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, or an immunogenic fragment thereof, underconditions to elicit an antibody response, b) isolating antibodies fromsaid animal, and c) screening the isolated antibodies with thepolypeptide, thereby identifying a polyclonal antibody whichspecifically binds to a polypeptide comprising an amino acid sequenceselected from the group consisting of SEQ ID NO:1-73.
 37. A polyclonalantibody produced by a method of claim
 36. 38. A composition comprisingthe polyclonal antibody of claim 37 and a suitable carrier.
 39. A methodof making a monoclonal antibody with the specificity of the antibody ofclaim 11, the method comprising: a) immunizing an animal with apolypeptide consisting of an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73, or an immunogenic fragment thereof, underconditions to elicit an antibody response, b) isolating antibodyproducing cells from the animal, c) fusing the antibody producing cellswith immorialized cells to form monoclonal antibody-producing hybridomacells, d) culturing the hybridoma cells, and e) isolating from theculture monoclonal antibody which specifically binds to a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-73.
 40. A monoclonal antibody produced by a method of claim39.
 41. A composition comprising the monoclonal antibody of claim 40 anda suitable carrier.
 42. The antibody of claim 11, wherein the antibodyis produced by screening a Fab expression library.
 43. The antibody ofclaim 11, wherein the antibody is produced by screening a recombinantimmunoglobulin library.
 44. A method of detecting a polypeptidecomprising an amino acid sequence selected from the group consisting ofSEQ ID NO:1-73 in a sample, the method comprising: a) incubating theantibody of claim 11 with a sample under conditions to allow specificbinding of the antibody and the polypeptide, and b) detecting specificbinding, wherein specific binding indicates the presence of apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73 in the sample.
 45. A method of purifying apolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73 from a sample, the method comprising: a)incubating the antibody of claim 11 with a sample under conditions toallow specific binding of the antibody and the polypeptide, and b)separating the antibody from the sample and obtaining the purifiedpolypeptide comprising an amino acid sequence selected from the groupconsisting of SEQ ID NO:1-73.
 46. A microarray wherein at least oneelement of the microarray is a polynucleotide of claim
 13. 47. A methodof generating an expression profile of a sample which containspolynucleotides, the method comprising: a) labeling the polynucleotidesof the sample, b) contacting the elements of the microarray of claim 46with the labeled polynucleotides of the sample under conditions suitablefor the formation of a hybridization complex, and c) quantifying theexpression of the polynucleotides in the sample.
 48. An array comprisingdifferent nucleotide molecules affixed in distinct physical locations ona solid substrate, wherein at least one of said nucleotide moleculescomprises a first oligonucleotide or polynucleotide sequencespecifically hybridizable with at least 30 contiguous nucleotides of atarget polynucleotide, and wherein said target polynucleotide is apolynucleotide of claim
 12. 49. An array of claim 48, wherein said firstoligonucleotide or polynucleotide sequence is completely complementaryto at least 30 contiguous nucleotides of said target polynucleotide. 50.An array of claim 48, wherein said first oligonucleotide orpolynucleotide sequence is completely complementary to at least 60contiguous nucleotides of said target polynucleotide.
 51. An array ofclaim 48, wherein said first oligonucleotide or polynucleotide sequenceis completely complementary to said target polynucleotide.
 52. An arrayof claim 48, which is a microarray.
 53. An array of claim 48, furthercomprising said target polynucleotide hybridized to a nucleotidemolecule comprising said first oligonucleotide or polynucleotidesequence.
 54. An array of claim 48, wherein a linker joins at least oneof said nucleotide molecules to said solid substrate.
 55. An array ofclaim 48, wherein each distinct physical location on the substratecontains multiple nucleotide molecules, and the multiple nucleotidemolecules at any single distinct physical location have the samesequence, and each distinct physical location on the substrate containsnucleotide molecules having a sequence which differs from the sequenceof nucleotide molecules at another distinct physical location on thesubstrate.
 56. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:1.
 57. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:2.
 58. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:3.
 59. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:4.
 60. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:5.
 61. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:6.
 62. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:7.
 63. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:8.
 64. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:9.
 65. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:10.
 66. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:11.
 67. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:12.
 68. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:13.
 69. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:14.
 70. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:15.
 71. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:16.
 72. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:17.
 73. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:18.
 74. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:19.
 75. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:20.
 76. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:21.
 77. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:22.
 78. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:23.
 79. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:24.
 80. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:25.
 81. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:26.
 82. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:27.
 83. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:28.
 84. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:29.
 85. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:30.
 86. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:31.
 87. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:32.
 88. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:33.
 89. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:34.
 90. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:35.
 91. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:36.
 92. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:37.
 93. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:38.
 94. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:39.
 95. A polypeptide ofclaim 1, comprising the amino acid sequence of SEQ ID NO:40.
 96. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:41.
 97. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:42.
 98. A polypeptide of claim 1, comprising the amino acidsequence of SEQ ID NO:43.
 99. A polypeptide of claim 1, comprising theamino acid sequence of SEQ ID NO:44.
 100. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:45.
 101. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:46.
 102. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:47.
 103. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:48.
 104. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:49.
 105. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:50.
 106. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:51.
 107. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:52.
 108. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:53.
 109. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:54.
 110. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:55.
 111. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:56.
 112. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:57.
 113. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:58.
 114. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:59.
 115. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:60.
 116. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:61.
 117. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:62.
 118. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:63.
 119. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:64.
 120. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:65.
 121. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:66.
 122. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:67.
 123. A polypeptide of claim 1, comprisingthe amino acid sequence of SEQ ID NO:68.
 124. A polypeptide of claim 1,comprising the amino acid sequence of SEQ ID NO:69.
 125. A polypeptideof claim 1, comprising the amino acid sequence of SEQ ID NO:70.
 126. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ IDNO:71.
 127. A polypeptide of claim 1, comprising the amino acid sequenceof SEQ ID NO:72.
 128. A polypeptide of claim 1, comprising the aminoacid sequence of SEQ ID NO:73.
 129. A polynucleotide of claim 12,comprising the polynucleotide sequence of SEQ ID NO:74.
 130. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:75.
 131. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:76.
 132. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:77.
 133. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:78.
 134. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:79.
 135. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:80.
 136. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:81.
 137. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:82.
 138. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:83.
 139. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:84.
 140. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:85.
 141. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:86.
 142. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:87.
 143. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:88.
 144. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:89.
 145. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:90.
 146. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:91.
 147. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:92.
 148. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:93.
 149. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:94.
 150. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:95.
 151. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:96.
 152. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:97.
 153. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:98.
 154. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:99.
 155. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:100.
 156. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:101.
 157. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:102.
 158. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:103.
 159. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:104.
 160. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:105.
 161. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:106.
 162. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:107.
 163. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:108.
 164. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:109.
 165. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:110.
 166. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:111.
 167. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:112.
 168. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:113.
 169. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:114.
 170. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:115.
 171. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:116.
 172. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:117.
 173. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:118.
 174. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:119.
 175. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:120.
 176. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:121.
 177. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:122.
 178. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:123.
 179. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:124.
 180. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:125.
 181. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:126.
 182. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:127.
 183. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:128.
 184. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:129.
 185. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:130.
 186. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:131.
 187. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:132.
 188. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:133.
 189. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:134.
 190. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:135.
 191. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:136.
 192. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:137.
 193. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:138.
 194. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:139.
 195. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:140.
 196. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:141.
 197. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:142.
 198. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:143.
 199. Apolynucleotide of claim 12, comprising the polynucleotide sequence ofSEQ ID NO:144.
 200. A polynucleotide of claim 12, comprising thepolynucleotide sequence of SEQ ID NO:145.
 201. A polynucleotide of claim12, comprising the polynucleotide sequence of SEQ ID NO:146.